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LAMP2A as a therapeutic target in Parkinson disease

Xilouri, Maria; Brekk, Oeystein Roed; Kirik, Deniz LU and Stefanis, Leonidas (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)
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author
organization
publishing date
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
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
2014-02-10 12:17:09
date last changed
2019-02-20 01:03:14
@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},
  keyword      = {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},
  volume       = {9},
  year         = {2013},
}