Activating Autophagy as a Therapeutic Strategy for Parkinson's Disease

CNS Drugs
Alan J Fowler, Charbel E-H Moussa

Abstract

Parkinson's disease is a progressive neurodegenerative disease characterized by Lewy body pathology of which the primary constituent is aggregated misfolded alpha-synuclein protein. Currently, there are no clinical therapies for treatment of the underlying alpha-synuclein dysfunction and accumulation, and the standard of care for patients with Parkinson's disease focuses only on symptom management, creating an immense therapeutic gap that needs to be filled. Defects in autophagy have been strongly implicated in Parkinson's disease. Here, we review evidence from human, mouse, and cell culture studies to briefly explain these defects in autophagy in Parkinson's disease and the necessity for autophagy to be carefully and precisely tuned to maintain neuron survival. We summarize recent experimental agents for treating alpha-synuclein accumulation in α-synuclein Parkinson's disease and related synucleinopathies. Most of the efforts for developing experimental agents have focused on immunotherapeutic strategies, but we discuss why those efforts are misplaced. Finally, we emphasize why increasing autophagy flux for alpha-synuclein clearance is the most promising therapeutic strategy. Activating autophagy has been successful in preclin...Continue Reading

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Citations

Dec 14, 2018·Frontiers in Aging Neuroscience·Guoxin ZhangTao Wang
Apr 2, 2019·Bioorganic & Medicinal Chemistry·Louis BornancinBernard Banaigs
Jun 20, 2021·Lancet Neurology·Nirosen VijiaratnamThomas Foltynie
Aug 28, 2021·Biology·Laura Lestón PinillaLuigi A De Girolamo

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Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

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