Protein misfolding in neurodegenerative diseases: implications and strategies
| Autor: | Hyunsun Park, Robert Hodgson, Gabrielle G Leblanc, Marc Baumann, Anjli Venkateswaran, John Dunlop, Alexander McCampbell, Judith Frydman, Ron R. Kopito, Antti Nurmi, Patrick Sweeney |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cognitive Neuroscience Druggability Disease Review Biology Mouse models 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Chaperones medicine Neurodegeneration Alpha-synuclein Drug discovery Autophagy medicine.disease 3. Good health 030104 developmental biology Proteostasis Proteasome chemistry Neurology (clinical) Neuroscience Biomarkers |
| Zdroj: | Translational Neurodegeneration |
| ISSN: | 2047-9158 |
| Popis: | A hallmark of neurodegenerative proteinopathies is the formation of misfolded protein aggregates that cause cellular toxicity and contribute to cellular proteostatic collapse. Therapeutic options are currently being explored that target different steps in the production and processing of proteins implicated in neurodegenerative disease, including synthesis, chaperone-assisted folding and trafficking, and degradation via the proteasome and autophagy pathways. Other therapies, like mTOR inhibitors and activators of the heat shock response, can rebalance the entire proteostatic network. However, there are major challenges that impact the development of novel therapies, including incomplete knowledge of druggable disease targets and their mechanism of action as well as a lack of biomarkers to monitor disease progression and therapeutic response. A notable development is the creation of collaborative ecosystems that include patients, clinicians, basic and translational researchers, foundations and regulatory agencies to promote scientific rigor and clinical data to accelerate the development of therapies that prevent, reverse or delay the progression of neurodegenerative proteinopathies. |
| Databáze: | OpenAIRE |
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