Beta amyloid protein: Jobs : Director, Center for Brain Health & Associate Professor or Professor of IMSD

Director, Center for Brain Health & Associate Professor or Professor of IMSD

Posted 10 Jul 2020

Employer

Florida Atlantic University

Location

Boca Raton, Florida

Contact

All applicants must apply electronically to the currently posted position (Director, Center for Brain Health & Associate Professor or Professor of Integrated Medical Science) on the Office of Human Resources' job website by completing the required online employment application and submitting the related documents. When completing the online application, please upload a cover letter, curriculum vitae, and copies of official transcripts scanned into an electronic format.

Any confidential letters of recommendation/references may be sent to Sara Greene, greenes@health.fau.edu.

A background check will be required for the candidate selected for this position. This position is subject to funding.

For more information and to apply, visit www.fau.edu/jobsand go to Apply Now (REQ08851).

Description

The Charles E. Schmidt College of Medicine, Florida Atlantic University (FAU), is seeking a world-class clinician scientist to develop an academically oriented program aimed at reducing the toll of Alzheimer's disease (AD) and related dementias in Florida and beyond. The ideal clinician scientist will be a national leader in deep phenotyping and deploying personalized approaches for the prevention, diagnosis, and treatment of the full spectrum of dementias.

Operating within an integrated health practice model, the clinician scientist will build and shape a comprehensive program in brain health, with possibilities for collaboration through partnerships with FAU centers and institutes, including the Louis and Anne Green Memory and Wellness Center, a dementia specific program providing supportive services to ~4,500 unique patients annually, and the Brain Institute, a university research pillar dedicated to the advancement of neuroscience research, education, and community outreach. Additional outstanding clinical and research partnerships are available through the Marcus Neuroscience Institute at Boca Raton Regional Hospital, Scripps Research Institute Florida, and the Max Planck Florida Institute for Neuroscience.

Florida Atlantic University is an equal opportunity/affirmative action/equal access institution and all qualified applicants will receive consideration without regard to race, color, religion, sex, sexual orientation, gender identity, national origin, disability status, protected veterans status or other protected status. Individuals with disabilities requiring accommodation, please call 561-297-3057. 711.

FAU is committed to the principles of engaged teaching, research and service.  All persons aspiring to achieve excellence in the practice of these principles are encouraged to apply.

Requirements

Minimum Qualification:

Experience:

• Board-certified neurologist, psychiatrist or neuropsychologist with expertise in Alzheimer's disease, and/or Lewy body dementia, and other dementias
• Academic credentials from an accredited institution that merit appointment at associate or full professor in the College of Medicine by the time of application
• Distinguished record in clinical translational research, and education
• Proven record of broad, progressive and substantive administrative leadership
• Experience in clinical trials research
• Experience in building diverse and multi-disciplinary teams
• Innovative program development leadership from a start-up phase
• Strong track record in external funding and program or center leadership, with active foundation, state, and/or federal research grant funding, in the areas of Alzheimer's disease, Lewy body dementia, or other dementias

Knowledge/Skills:

• Knowledge of trends and issues in integrative health with respect to the prevention and treatment of dementias
• Ability to engage with community and establish effective partnerships in an academic environment
• Rigorous with data and metrics
• Outstanding communication skills
• Budgetary and financial management skills
• Ability to build and sustain effective teams, including inter-professional and interdisciplinary
• Management skills that include collegiality and respect
• Excellence in problem solving
• Outstanding communication skills, including effective communication in a culturally and ethnically diverse community

Characteristics:

• Commitment to diversity and inclusion as a means of achieving institutional excellence
• Ability to communicate effectively in a culturally and ethnically diverse community
• Emotional intelligence
• Divergent thinking
• Effective decision maker
• Collaborative
• Transparent
• Community-focused
• Entrepreneurial
• Commitment to excellence in clinical practice, teaching, research, and community engagement/service
• Capacity to advance strategic initiatives and achieve targeted goals
• Commitment to building and bridging partnership

This article originally appeared in the "  https://www.alzforum.org/jobs/director-center-brain-health-associate-professor-or-professor-imsd   " and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice. 

Role of Beta Amyloid Peptide: Jobs : Postdoctoral Fellow

Postdoctoral Fellow

Posted 15 Jul 2020

Employer

Center for Alzheimer's and Neurodegenerative Diseases at University of Texas Southwestern Medical Center

Location

Dallas, Texas

Principal Investigator

Rachel Bailey

Contact

Interested applicants should contact Dr. Bailey at Rachel.Bailey@UTSouthwestern.edu and provide a brief cover letter, a CV, and contact info for three references.

Description

A postdoctoral training position is immediately available in the laboratory of Dr. Rachel Bailey in the Center for Alzheimer's & Neurodegenerative Diseases at UT Southwestern Medical Center to study research using adeno-associated virus (AAV) gene therapy for the treatment of neurodegenerative diseases. The laboratory has several gene therapy projects with the eventual goal of translating research to a Phase I clinical trial. The position will perform specialized research experiments in cultured cells and small animals.

UT Southwestern Medical Center is an Affirmative Action/Equal Opportunity Employer. Women, minorities, veterans and individuals with disabilities are encouraged to apply. Information on UT's postdoctoral training program and benefits can be found in its postdoc handbook or at http://www.utsouthwestern.edu/postdocs.

Requirements

Candidates must hold a Ph.D. degree. Interested candidates must have 1) a strong background in biochemistry, cell biology, molecular biology, or a related discipline, 2) publication and grant writing record, 3) scientific curiosity and the desire and ability to work independently.

Experience with disease models and genomic approaches (i.e. RNA-seq) are a plus.

This article originally appeared in the " https://www.alzforum.org/jobs/postdoctoral-fellow-10 " and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice. 

Role of Beta Amyloid Peptide: Jobs : Postdoctoral Associate

Postdoctoral Associate

Posted 19 Jun 2020

Employer

Cornell University

Location

Ithaca, New York

Principal Investigator

Fenghua Hu

Contact

Interested candidates should send a copy of CV, statement of research interests and three letters of references to fenghualab@gmail.com.

Description

Postdoctoral positions are currently available in the Hu lab to study molecular and cellular mechanisms of neurodegeneration. The lab is seeking candidates who have a strong background in biochemistry, molecular biology, cell biology, or mouse genetics with interests in neurodegeneration. Please visit its website, https://hu.wicmb.cornell.edu/, for details. 

Requirements

Ph.D. in cell biology, biochemistry or neuroscience

This article originally appeared in the " https://www.alzforum.org/jobs/postdoctoral-associate     " and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice. 

Role of Beta Amyloid Peptide: Jobs : Director, Division of Aging Biology

Director, Division of Aging Biology

Posted 22 Jun 2020

Employer

NIH, National Institute on Aging

Location

Bethesda, Maryland

Contact

Please send a cover letter, current curriculum vitae, including bibliography, a vision statement, and a statement that addresses the specific qualification requirements listed above (please limit both statements to two pages each), and three letters of reference to Cheryl Caponiti (caponitc@mail.nih.gov). NIA plans to have the position open until filled.

You may contact Cheryl Caponiti at caponitc@mail.nih.gov for more information about this vacancy.

Description

The National Institute on Aging is seeking an innovative scientific leader to serve as Director of its extramural Division of Aging Biology (DAB).  The position reports directly to the NIA director.

Over the last two decades research on the biological mechanisms of aging has expanded almost exponentially. It is now widely acknowledged that the mechanisms of aging determine the quality of health and function, as well as contributing to the pathogenesis and modulating the progression of most chronic diseases. A greater understanding of the aging process is a fundamental step toward identifying new preventive and therapeutic strategies that can improve the human life span and reduce the burden of age-related chronic diseases, with large benefits to individuals and society. The DAB has a fundamental role in the accomplishment of this goal with a focus on advancing research on aging by providing funding to support to academic institutions across the U.S. through grants and programs that investigate the basic biology of aging at the molecular, cellular, and organismal level in a variety of model systems. Through its funding programs, DAB supports and ensures continuity and stability of ongoing lines of basic research in aging biology while encouraging and facilitating the emergence of new ideas, concepts, and technologies, as well as new organizational models for aging research. The DAB portfolio is exceptionally broad, covering all research fields of basic aging biology, including fundamental genetic, molecular, and cellular mechanisms of aging, the study of aging in different model systems including comparative studies, search for mechanisms of longevity, and the testing of behavioral and pharmacological treatments in model systems for improvement of health-span and lifespan.

Because of the strong translational nature of the topic addressed, the work of DAB is strongly connected with the research conducted by other components of NIA, as well as other NIH institutes, other academic institutions and medical specialties, with many opportunities for collaborative projects and cross-fertilization of different areas of biological, behavioral, and medical research. These goals of the DAB are implemented through extramural grants, cooperative agreements, collaborative projects, contracts, and other activities.  Additional information regarding the DAB is available at the following website: https://www.nia.nih.gov/research/dab.

The division director serves as the scientific and administrative leader of the DAB and provides scientific expertise and strategic vision for the DAB portfolio, including identification of emerging new directions for basic research in aging biology, support of novel technologies, and development of collaborative programs with other NIA extramural divisions, the NIA Intramural Research Program (IRP), and other NIH Institutes. The Division Director oversees all scientific and administrative operations of the DAB and has responsibility for: (1) scientific planning and strategy, (2) operational administration of the division; (3) oversight of all the division's grants and cooperative agreement research activities; (4) budget management, and (5) working with and advising NIA senior leadership on the development and implementation of long-range strategic, scientific, facility and business plans for the division. The division director oversees approximately 17 scientific and administrative staff and an operating budget of $375,000 and oversees extramural research funding of approximately $313 million.

Salary/Benefits: This position will be filled under a Title 42 excepted service appointment.  Salary is competitive and will be commensurate with the experience of the candidate. A recruitment or relocation bonus may be available, and relocation expenses may be paid. A full package of federal Civil Service benefits is available including retirement, health and life insurance, long term care insurance, leave, and a Thrift Savings Plan (401K equivalent). The successful candidate may be subject to a background investigation and public financial disclosure requirements.  All employees of the Federal Government are subject to the conflict of interest statutes and regulations, including Standards of Ethical Conduct.

DHHS and NIH are Equal Opportunity Employers The NIH is dedicated to building a diverse community in its training and employment programs.

 

 

Requirements

The successful candidate must have an M.D. and/or Ph.D. or equivalent degree in a discipline relevant to biology and have extensive training and experience in research on the biology of aging research or related disciplines that can be applied to aging research. The successful candidate will have experience in collaborative research as documented in publications and more generally will have a history of publications that reflect experience in the requirements of the position. In addition, the candidate must have demonstrated administrative skills in supervising scientific and administrative staff, in overseeing complex research programs, and in collaborating and enhancing partnerships in the aging research community. The candidate should also have experience in developing strategic goals, managing human resources and budgetary planning and management. Eligible candidates who are also active researchers may establish a small laboratory research program in the NIA IRP.

This article originally appeared in the " https://www.alzforum.org/jobs/director-division-aging-biology " and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice. 

Role of Beta Amyloid Peptide: Jobs :Staff Scientist

Staff Scientist

Posted 22 Jun 2020

Employer

National Institutes of Health, National Institutes of Neurological Disorders and Stroke

Location

Bethesda, Maryland

Principal Investigator

John Ngai

Contact

Application packages are to include a Curriculum Vitae with bibliography, statement of research interests and a list of three references to: Nhi Floyd, Senior Administrative Officer, NINDS at NINDSBrainJobs@nih.gov (phone: 301-443-8013). Please include a description of mentoring and outreach activities, especially those that are relevant to the specific areas of study of the Molecular Neurobiology Section. Salary is commensurate with experience and a full package of Civil Service benefits is available. All information provided by applicants will remain confidential and will not be released outside the NINDS search process without a signed release from candidates.

E-mail a single PDF document to Nhi Floyd at NINDSBrainJobs@nih.gov containing the following:

• Curriculum Vitae with bibliography
• One-page statement of your philosophy of successful operation of a research laboratory
• Contact information for at least three references

All employees are subject to a background investigation.

Description

A staff scientist position is available in John Ngai's laboratory in the Molecular Neurobiology Section at the National Institutes of Health. The focus of this position is to oversee studies focused on understanding the genetic, epigenetic, and cell-signaling pathways underlying neural development and adult stem cell-mediated regeneration using the mouse peripheral olfactory system as the primary model. These studies will use a combination of approaches including single-cell transcriptomic and epigenomic analyses, mouse transgenic and other genetic approaches, viral transduction, immunohistochemistry, multiplexed RNA in situ hybridization, and confocal and other advanced light microscopy techniques. Our long-term goal is to elucidate the molecular determinants regulating the progression of cells in a developmental or regenerating pathway during the construction or repair of neural circuits.

At NIH, the staff scientist is a central member of research teams, who typically runs the scientific and teaching aspects of a Principal Investigator's research program. He/she would provide direct supervision for two or three students and/or postdocs. Together with the PI, he/she would steer the long-term direction of the research group. The opportunity also exists for the Staff Scientist to conduct his/her own studies in the above research area.

The successful candidate will be offered salary and benefits commensurate with experience and accomplishments. The appointment would be through the Title 42 mechanism - http://hr.od.nih.gov/benefits/pay/default.htm.

See https://braininitiative.nih.gov/ for further information.

Requirements

Applicants should have a Ph.D. degree (or equivalent) in molecular, cellular, and/or developmental biology, genomics, computational biology, or equivalent field and significant experience in developmental/regenerative biology. He/she should have publications demonstrating these skills, as well as expertise in the area of genomics research. Fluent command of both spoken and written English is imperative.

The applicant should have experience in supervising trainees in laboratory research and must have a track record indicative of innovative thinking.

This article originally appeared in the " https://www.alzforum.org/jobs/staff-scientist " and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice. 

Role of Beta Amyloid Peptide: Jobs : Executive Medical Director Alzheimer's Disease, US

Executive Medical Director Alzheimer's Disease, US Medical Affairs

Posted 23 Jun 2020

Employer

Biogen

Contact

judy.lewallen@biogen.com

Description

This position leads and oversees all the U.S. launch and post-launch activities for Alzheimer's disease. Reporting to the VP-U.S. and Global Alzheimer Medical, the position is responsible for developing and implementing the launch strategy, including the Alzheimer's Disease Medical Science Liaison team and medical directors.

The US Medical Lead represents medical in the Alzheimer's Disease U.S. Leadership Team (US ADLT) and is an ad hoc member of the US Leadership Team (USLT) and in that capacity, has frequent interactions with Executive management. This role oversees a team currently consisting of medical directors and medical science liaisons. This individual is responsible for developing the strategy in alignment with the cross-functional partners and ensuring that the metrics and goals are met across the US AD medical organization.

• Accountable for the development of the U.S. Launch and post-launch strategy and tactical plan, including developing measurable metrics.
• Sits on the US ADLT and Alzheimer's Disease Medical Leadership team and she/he is the key point of contact for internal US-related interactions with senior management and externally with the key medical experts and other key stakeholders.
• Accountable for ensuring production of highest quality local data generation plan in alignment with the cross-functional stakeholders and overall Alzheimer's Disease Medical strategy.
• Accountable for attracting, retaining, developing and supervising a team of US medical affairs Alzheimer's Disease experts both in the Medical Director office and MSL team as business needs require.

Requirements

At least 10 years in pharmaceutical industry with experience in leading U.S. drug launch activities in medical affairs (neurology preferred).

Experience managing and developing large medical organizations.

Excellent written and oral English communication skills using common business technologies (i.e. Word, PowerPoint).

Demonstrated leadership capabilities including the ability to solve problems effectively in a highly collaborative matrix environment.

M.D., or Ph.D., ideally with training in neurology.

This article originally appeared in the "   https://www.alzforum.org/jobs/executive-medical-director-alzheimers-disease-us-medical-affairs   " and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice. 

Role of Beta Amyloid Peptide: Research Paper : Congenic expression of poly-GA but not poly-PR in mice triggers selective neuron loss and interferon responses found in C9orf72 ALS

Abstract

Expansion of a (G4C2)n repeat in C9orf72 causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the link of the five repeat-encoded dipeptide repeat (DPR) proteins to neuroinflammation, TDP-43 pathology, and neurodegeneration is unclear. Poly-PR is most toxic in vitro, but poly-GA is far more abundant in patients. To directly compare these in vivo, we created congenic poly-GA and poly-PR mice. 40% of poly-PR mice were affected with ataxia and seizures, requiring euthanasia by 6 weeks of age. The remaining poly-PR mice were asymptomatic at 14 months of age, likely due to an 80% reduction of the transgene mRNA in this subgroup. In contrast, all poly-GA mice showed selective neuron loss, inflammation, as well as muscle denervation and wasting requiring euthanasia before 7 weeks of age. In-depth analysis of peripheral organs and blood samples suggests that peripheral organ failure does not drive these phenotypes. Although transgene mRNA levels were similar between poly-GA and affected poly-PR mice, poly-GA aggregated far more abundantly than poly-PR in the CNS and was also found in skeletal muscle. In addition, TDP-43 and other disease-linked RNA-binding proteins co-aggregated in rare nuclear inclusions in the hippocampus and frontal cortex only in poly-GA mice. Transcriptome analysis revealed activation of an interferon-responsive pro-inflammatory microglial signature in end-stage poly-GA but not poly-PR mice. This signature was also found in all ALS patients and enriched in C9orf72 cases. In summary, our rigorous comparison of poly-GA and poly-PR toxicity in vivo indicates that poly-GA, but not poly-PR at the same mRNA expression level, promotes interferon responses in C9orf72 disease and contributes to TDP-43 abnormalities and neuron loss selectively in disease-relevant regions.

Keywords: ALS; C9orf72; FTD; Interferon; Microglia; Mouse model; Neurodegeneration.

This article originally appeared in the "  https://pubmed.ncbi.nlm.nih.gov/32562018/  " and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice. 

Role of Beta Amyloid Peptide: Research Paper : Role of alpha-synuclein phosphorylation at Serine 129 in methamphetamine-induced neurotoxicity in vitro and in vivo

Abstract

The phosphorylation and aggregation of alpha-synuclein (α-Syn) play a key role in methamphetamine (METH)-induced dopaminergic neurotoxicity. The exact mechanism underlying the interaction between METH-induced neurotoxicity and α-Syn was poorly clarified. We aimed to figure out the role of serine 129 phosphorylation (pS129) of α-Syn on its aggregation and neurotoxicity in vitro and in vivo. In this study, we examined pS129 α-Syn expression in vitro and in vivo at the protein phosphorylation and genetic levels and evaluated its effect on METH-induced neurotoxicity. Here, we found that pS129 α-Syn was significantly increased after METH treatment; moreover, the neuronal α-Syn aggregation and apoptosis caused by METH exposure were significantly attenuated after inhibiting α-Syn phosphorylation. We demonstrate that pS129 α-Syn contributes to the aggregation of α-Syn, and that phosphorylated and aggregated forms of α-Syn play an important role in METH-induced neurotoxicity in dopaminergic neurons and SH-SY5Y cells, supporting a potential insight into the treatment of METH-induced neurotoxicity.

This article originally appeared in the "   https://pubmed.ncbi.nlm.nih.gov/32568772/   " and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice. 

Role of Beta Amyloid Peptide: Parkinson's disease: etiopathogenesis and treatment

Abstract

The concept of 'idiopathic' Parkinson's disease (PD) as a single entity has been challenged with the identification of several clinical subtypes, pathogenic genes and putative causative environmental agents. In addition to classic motor symptoms, non-motor manifestations (such as rapid eye movement sleep disorder, anosmia, constipation and depression) appear at prodromic/premotor stage and evolve, along with cognitive impairment and dysautonomia, as the disease progresses, often dominating the advanced stages of the disease. The key molecular pathogenic mechanisms include α-synuclein misfolding and aggregation, mitochondrial dysfunction, impairment of protein clearance (associated with deficient ubiquitin-proteasome and autophagy-lysosomal systems), neuroinflammation and oxidative stress. The involvement of dopaminergic as well as noradrenergic, glutamatergic, serotonergic and adenosine pathways provide insights into the rich and variable clinical phenomenology associated with PD and the possibility of alternative therapeutic approaches beyond traditional dopamine replacement therapies.One of the biggest challenges in the development of potential neuroprotective therapies has been the lack of reliable and sensitive biomarkers of progression. Immunotherapies such as the use of vaccination or monoclonal antibodies directed against aggregated, toxic α-synuclein.as well as anti-aggregation or protein clearance strategies are currently investigated in clinical trials. The application of glucagon-like peptide one receptor agonists, specific PD gene target agents (such as GBA or LRRK2 modifiers) and other potential disease modifying drugs provide cautious optimism that more effective therapies are on the horizon. Emerging therapies, such as new symptomatic drugs, innovative drug delivery systems and novel surgical interventions give hope to patients with PD about their future outcomes and prognosis.

Keywords: clinical neurology.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

This article originally appeared in the "  https://pubmed.ncbi.nlm.nih.gov/32576618/    " and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice. 

Role of Beta Amyloid Peptide: Research Paper : Congenic expression of poly-GA but not poly-PR in mice triggers selective neuron loss and interferon responses found in C9orf72 ALS

Abstract

Expansion of a (G4C2)n repeat in C9orf72 causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the link of the five repeat-encoded dipeptide repeat (DPR) proteins to neuroinflammation, TDP-43 pathology, and neurodegeneration is unclear. Poly-PR is most toxic in vitro, but poly-GA is far more abundant in patients. To directly compare these in vivo, we created congenic poly-GA and poly-PR mice. 40% of poly-PR mice were affected with ataxia and seizures, requiring euthanasia by 6 weeks of age. The remaining poly-PR mice were asymptomatic at 14 months of age, likely due to an 80% reduction of the transgene mRNA in this subgroup. In contrast, all poly-GA mice showed selective neuron loss, inflammation, as well as muscle denervation and wasting requiring euthanasia before 7 weeks of age. In-depth analysis of peripheral organs and blood samples suggests that peripheral organ failure does not drive these phenotypes. Although transgene mRNA levels were similar between poly-GA and affected poly-PR mice, poly-GA aggregated far more abundantly than poly-PR in the CNS and was also found in skeletal muscle. In addition, TDP-43 and other disease-linked RNA-binding proteins co-aggregated in rare nuclear inclusions in the hippocampus and frontal cortex only in poly-GA mice. Transcriptome analysis revealed activation of an interferon-responsive pro-inflammatory microglial signature in end-stage poly-GA but not poly-PR mice. This signature was also found in all ALS patients and enriched in C9orf72 cases. In summary, our rigorous comparison of poly-GA and poly-PR toxicity in vivo indicates that poly-GA, but not poly-PR at the same mRNA expression level, promotes interferon responses in C9orf72 disease and contributes to TDP-43 abnormalities and neuron loss selectively in disease-relevant regions.

Keywords: ALS; C9orf72; FTD; Interferon; Microglia; Mouse model; Neurodegeneration.

Conflict of interest statement

DE and TA hold a patent (US10066007B2) on "Dipeptide-repeat proteins as therapeutic target in neurodegenerative diseases with hexanucleotide repeat expansion". DE and QZ applied for a patent on active vaccination targeting DPRs in C9orf72 ALS/FTD.

This article originally appeared in the "  https://pubmed.ncbi.nlm.nih.gov/32562018/  " and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.