LAMP2A as a therapeutic target in Parkinson disease
(2013) In Autophagy 9(12). p.2166-2168- Abstract
- Abnormal aggregation of SNCA/-synuclein plays a crucial role in Parkinson disease (PD) pathogenesis. SNCA levels determine its toxicity, and its accumulation, even to a small extent, may be a risk factor for neurodegeneration. One of the main pathways for SNCA degradation is chaperone-mediated autophagy (CMA), a selective form of autophagy, while aberrant SNCA may act as a CMA inhibitor. In the current punctum we summarize our recent data showing that induction of CMA, via overexpression of the protein controlling its rate-limiting step, the lysosomal receptor LAMP2A, effectively decreases SNCA levels and ameliorates SNCA-induced neurodegeneration, both in neuronal cell culture systems and in the rat brain. Such findings suggest that... (More)
- Abnormal aggregation of SNCA/-synuclein plays a crucial role in Parkinson disease (PD) pathogenesis. SNCA levels determine its toxicity, and its accumulation, even to a small extent, may be a risk factor for neurodegeneration. One of the main pathways for SNCA degradation is chaperone-mediated autophagy (CMA), a selective form of autophagy, while aberrant SNCA may act as a CMA inhibitor. In the current punctum we summarize our recent data showing that induction of CMA, via overexpression of the protein controlling its rate-limiting step, the lysosomal receptor LAMP2A, effectively decreases SNCA levels and ameliorates SNCA-induced neurodegeneration, both in neuronal cell culture systems and in the rat brain. Such findings suggest that modulation of LAMP2A and, consequently, CMA, represents a viable therapeutic target for PD and other synucleinopathies where SNCA accumulation and aggregation plays a fundamental role. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4269033
- author
- Xilouri, Maria ; Brekk, Oeystein Roed ; Kirik, Deniz LU and Stefanis, Leonidas
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- alpha-synuclein, chaperone-mediated autophagy, dopaminergic system, LAMP2A, neurotoxicity, Parkinson disease, substantia nigra
- in
- Autophagy
- volume
- 9
- issue
- 12
- pages
- 2166 - 2168
- publisher
- Landes Bioscience
- external identifiers
-
- wos:000328299800023
- scopus:84890829178
- pmid:24145820
- ISSN
- 1554-8635
- DOI
- 10.4161/auto.26451
- language
- English
- LU publication?
- yes
- id
- 597193b7-99ff-4062-af28-57fea0d68af2 (old id 4269033)
- date added to LUP
- 2016-04-01 09:49:29
- date last changed
- 2022-04-27 07:44:58
@misc{597193b7-99ff-4062-af28-57fea0d68af2, abstract = {{Abnormal aggregation of SNCA/-synuclein plays a crucial role in Parkinson disease (PD) pathogenesis. SNCA levels determine its toxicity, and its accumulation, even to a small extent, may be a risk factor for neurodegeneration. One of the main pathways for SNCA degradation is chaperone-mediated autophagy (CMA), a selective form of autophagy, while aberrant SNCA may act as a CMA inhibitor. In the current punctum we summarize our recent data showing that induction of CMA, via overexpression of the protein controlling its rate-limiting step, the lysosomal receptor LAMP2A, effectively decreases SNCA levels and ameliorates SNCA-induced neurodegeneration, both in neuronal cell culture systems and in the rat brain. Such findings suggest that modulation of LAMP2A and, consequently, CMA, represents a viable therapeutic target for PD and other synucleinopathies where SNCA accumulation and aggregation plays a fundamental role.}}, author = {{Xilouri, Maria and Brekk, Oeystein Roed and Kirik, Deniz and Stefanis, Leonidas}}, issn = {{1554-8635}}, keywords = {{alpha-synuclein; chaperone-mediated autophagy; dopaminergic system; LAMP2A; neurotoxicity; Parkinson disease; substantia nigra}}, language = {{eng}}, number = {{12}}, pages = {{2166--2168}}, publisher = {{Landes Bioscience}}, series = {{Autophagy}}, title = {{LAMP2A as a therapeutic target in Parkinson disease}}, url = {{http://dx.doi.org/10.4161/auto.26451}}, doi = {{10.4161/auto.26451}}, volume = {{9}}, year = {{2013}}, }