What lysosomes actually tell us about Parkinson’s disease?
Abstract
Parkinson's disease is a common neurodegenerative disorder of unknown origin mainly characterized by the loss of neuromelanin-containing dopaminergic neurons in the substantia nigra pars compacta and the presence of intraneuronal proteinaceous inclusions called Lewy bodies. Lysosomes are dynamic organelles that degrade, in a controlled manner, cellular components delivered via the secretory, endocytic, autophagic and phagocytic membrane-trafficking pathways. Increasing amounts of evidence suggest a central role of lysosomal impairment in PD aetiology. This review provides an update on how genetic evidence support this connection and highlights how the neuropathologic and mechanistic evidence might relate to the disease process in sporadic forms of Parkinson's disease. Finally, we discuss the influence of ageing on lysosomal impairment and PD aetiology and therapeutic strategies targeting lysosomal function.
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Similar CTSD changes in fibroblasts carrying the ATP13A2 mutation in Parkinson disease were reversed by normalizing lysosomal pH with acidic nanoparticles.
“Similar CTSD changes seen in fibroblasts carrying the ATP13A2 mutation in Parkinson disease (Bourdenx and Dehay, 2016) were reversed by normalizing lysosomal pH with acidic nanoparticles”
From Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99) (2019) · cites this paper as Bourdenx and Dehay, 2016
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Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99)
Jiang, Y., Sato, Y., Im, E., Berg, M., Bordi, M., Darji, S., Kumar, A., Mohan, P. S., Bandyopadhyay, U., Diaz, A., et al. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.0578-19.2019 · Cited by 166 · see citing works
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- Authors
- Bourdenx, M., & Dehay, B.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Dehay, Benjamin
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 32
- Pages
- 140-149
- ISSN
- 1568-1637 (ISSN-L)
- OpenAlex
- W2293020656
- Cited by
- 26
- References
- 7
- Citations by year
- 2026: 1 · 2025: 4 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 2
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ageing Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Marie Curie Reintegration (FP7- PEOPLE-2009-ERG256303)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- Parkinson's disease, lysosomes, lysosomal dysfunction, Lewy bodies, dopaminergic neurons, substantia nigra, autophagy, endocytosis, phagocytosis, membrane trafficking, genetic risk factors, aging, neurodegeneration
- MeSH terms
- Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Aging, Autophagy, Humans, Lysosomes, Melanins, Nerve Degeneration, Parkinson Disease, Substantia Nigra, Lewy Bodies, Vesicular Transport Proteins, Dopaminergic Neurons
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