ReviewFrontiers in cell and developmental biology2020
Current Evidence for a Bidirectional Loop Between the Lysosome and Alpha-Synuclein Proteoforms.
Review in Frontiers in cell and developmental biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Organelle-Targeted Nanotherapeutics for Parkinson's Disease: From Pathogenesis to Preclinical Strategies and Translational Challenges.International journal of nanomedicine · 2026Review
- Research progress on the α-synuclein-lysosome axis in Parkinson's disease: molecular mechanisms of protein aggregation, autophagy dysfunction, and therapeutic targeting.Frontiers in neuroscience · 2026Review
- Article
- Biological definitions of synucleinopathies should be anchored in clinical trajectories and encompass the complex biology of the disease.Journal of Parkinson's disease · 2025Review
- BSCL2 and CDK5 are two genes associated with circadian rhythm disturbance in Parkinson's disease.Scientific reports · 2025Article
- Comparative study of autonomic dysfunction between Parkinson's disease with LRRK2, PRKN, and GBA mutations.Frontiers in neurology · 2025Article
- A critical appraisal of ferroptosis in Alzheimer's and Parkinson's disease: new insights into emerging mechanisms and therapeutic targets.Frontiers in pharmacology · 2024Review
- Genetics and Pathogenesis of Parkinson's Syndrome.Annual review of pathology · 2023Review
- A Mouse Model to Test Novel Therapeutics for Parkinson's Disease: an Update on the Thy1-aSyn ("line 61") Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- The ANeED study - ambroxol in new and early dementia with Lewy bodies (DLB): protocol for a phase IIa multicentre, randomised, double-blinded and placebo-controlled trial.Frontiers in aging neuroscience · 2023Article
- Role of Ubiquitin-Proteasome and Autophagy-Lysosome Pathways in α-Synuclein Aggregate Clearance.Molecular neurobiology · 2022Review
- Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model.EBioMedicine · 2022Article
- Dysautonomia in Parkinson's Disease: Impact of Glucocerebrosidase Gene Mutations on Cardiovascular Autonomic Control.Frontiers in neuroscience · 2022Article
- Contribution of Autophagy-Lysosomal Pathway in the Exosomal Secretion of Alpha-Synuclein and Its Impact in the Progression of Parkinson's Disease.Frontiers in molecular neuroscience · 2022Review
- The role of the endolysosomal pathway in α-synuclein pathogenesis in Parkinson's disease.Frontiers in cellular neuroscience · 2022Review
- Review
- Translocation of TMEM175 Lysosomal Potassium Channel to the Plasma Membrane by Dynasore Compounds.International journal of molecular sciences · 2021Article
- Targeting α-Synuclein in Parkinson's Disease by Induced Pluripotent Stem Cell Models.Frontiers in neurology · 2021Review
- Viral alpha-synuclein knockdown prevents spreading synucleinopathy.Brain communications · 2021Article
- Mimicking the Mammalian Plasma Membrane: An Overview of Lipid Membrane Models for Biophysical Studies.Biomimetics (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cumulative evidence collected in recent decades suggests that lysosomal dysfunction contributes to neurodegenerative diseases, especially if amyloid proteins are involved. Among these, alpha-synuclein (aSyn) that progressively accumulates and aggregates in Lewy bodies is undisputedly a main culprit in Parkinson disease (PD) pathogenesis. Lysosomal dysfunction is evident in brains of PD patients, and mutations in lysosomal enzymes are a major risk factor of PD. At first glance, the role of protein-degrading lysosomes in a disease with pathological protein accumulation seems obvious and should guide the development of straightforward and rational therapeutic targets. However, our review demonstrates that the story is more complicated for aSyn. The protein can possess diverse posttranslational modifications, aggregate formations, and truncations, all of which contribute to a growing known set of proteoforms. These interfere directly or indirectly with lysosome function, reducing their own degradation, and thereby accelerating the protein aggregation and disease process. Conversely, unbalanced lysosomal enzymatic processes can produce truncated aSyn proteoforms that may be more toxic and prone to aggregation. This highlights the possibility of enhancing lysosomal function as a treatment for PD, if it can be confirmed that this approach effectively reduces harmful aSyn proteoforms and does not produce novel, toxic proteoforms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.