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2017 ; 10
(ä): 82
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Post-translational Modifications and Protein Quality Control in Motor Neuron and
Polyglutamine Diseases
#MMPMID28408866
Sambataro F
; Pennuto M
Front Mol Neurosci
2017[]; 10
(ä): 82
PMID28408866
show ga
Neurodegenerative diseases, including motor neuron and polyglutamine (polyQ)
diseases, are a broad class of neurological disorders. These diseases are
characterized by neuronal dysfunction and death, and by the accumulation of toxic
aggregation-prone proteins in the forms of inclusions and micro-aggregates.
Protein quality control is a cellular mechanism to reduce the burden of
accumulation of misfolded proteins, a function that results from the coordinated
actions of chaperones and degradation systems, such as the ubiquitin-proteasome
system (UPS) and autophagy-lysosomal degradation system. The rate of turnover,
aggregation and degradation of the disease-causing proteins is modulated by
post-translational modifications (PTMs), such as phosphorylation, arginine
methylation, palmitoylation, acetylation, SUMOylation, ubiquitination, and
proteolytic cleavage. Here, we describe how PTMs of proteins linked to motor
neuron and polyQ diseases can either enhance or suppress protein quality control
check and protein aggregation and degradation. The identification of molecular
strategies targeting these modifications may offer novel avenues for the
treatment of these yet incurable diseases.