Developing Therapies for Neurodegenerative Disorders: Insights from Protein Aggregation and Cellular Stress Responses.
Annual review of cell and developmental biology
MetadataShow full item record
Mallucci, G., Klenerman, D., & Rubinsztein, D. (2020). Developing Therapies for Neurodegenerative Disorders: Insights from Protein Aggregation and Cellular Stress Responses.. Annual review of cell and developmental biology, 36 165-189. https://doi.org/10.1146/annurev-cellbio-040320-120625
As the world's population ages, neurodegenerative disorders are poised to become the commonest cause of death. Despite this, they remain essentially untreatable. Characterized pathologically both by the aggregation of disease-specific misfolded proteins and by changes in cellular stress responses, to date, therapeutic approaches have focused almost exclusively on reducing misfolded protein load-notably amyloid beta (Aβ) in Alzheimer's disease. The repeated failure of clinical trials has led to despondency over the possibility that these disorders will ever be treated. We argue that this is in fact a time for optimism: Targeting various generic stress responses is emerging as an increasingly promising means of modifying disease progression across these disorders. New treatments are approaching clinical trials, while novel means of targeting aggregates could eventually act preventively in early disease.
Lysosomes, Animals, Humans, Neurodegenerative Diseases, Stress, Physiological, Unfolded Protein Response, Protein Aggregates, Autophagosomes
We are grateful for funding from the UK Dementia Research Institute (funded by the MedicalResearch Council UK, Alzheimer’s Research UK, and the Alzheimer’s Society) (G.R.M., D.K.,and D.C.R.); the Cambridge Centre for Parkinson-Plus (G.R.M. and D.C.R.); the European Re-search Council, the Medical Research Council, the Joint Programme Neurodegenerative Disease,the Centres of Excellence in Neurodegeneration, and the Wellcome Trust Collaborative Award(G.R.M.); the Roger de Spoelberch Foundation, Alzheimer’s Research UK, and the National In-stitute for Health Research Cambridge Biomedical Research Centre (D.C.R.); and The RoyalSociety (D.K.).
Royal Society (RP150066)
ECH2020 EUROPEAN RESEARCH COUNCIL (ERC) (647479)
Wellcome Trust (via MRC) (201487/Z/16/Z)
UK Dementia Research Institute (DRICam17/18)
Embargo Lift Date
External DOI: https://doi.org/10.1146/annurev-cellbio-040320-120625
This record's URL: https://www.repository.cam.ac.uk/handle/1810/311394
All rights reserved