α-Synuclein phosphorylation as a therapeutic target in Parkinson’s disease
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Steven P. Braithwaite
,
Jeffry B. Stock
Abstract
Phosphorylation is a key post-translational modification necessary for normal cellular signaling and, therefore, lies at the heart of cellular function. In neurodegenerative disorders, abnormal hyperphosphorylation of pathogenic proteins is a common phenomenon that contributes in important ways to the disease process. A prototypical protein that is hyperphosphorylated in the brain is α-synuclein (α-syn) – found in Lewy bodies and Lewy neurites – the pathological hallmarks of Parkinson’s disease (PD) and other α-synucleinopathies. The genetic linkage of α-syn to PD as well as its pathological association in both genetic and sporadic cases have made it the primary protein of interest. In understanding how α-syn dysfunction occurs, increasing focus is being placed on its abnormal aggregation and the contribution of phosphorylation to this process. Studies of both the kinases and phosphatases that regulate α-syn phosphorylation are beginning to reveal the roles of this post-translational modification in disease pathogenesis. Modulation of α-syn phosphorylation may ultimately prove to be a viable strategy for disease-modifying therapeutic interventions. In this review, we explore mechanisms related to α-syn phosphorylation, its biophysical and functional consequences, and its role in neurodegeneration.
©2012 by Walter de Gruyter Berlin Boston
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Articles in the same Issue
- The role of androgens in regulating emotional state and aggressive behavior
- Role of stem cells in the regeneration and repair of peripheral nerves
- Interferon regulatory factor 1 regulation of oligodendrocyte injury and inflammatory demyelination
- Phosphoinositide 3-kinase enhancer (PIKE) in the brain: is it simply a phosphoinositide 3-kinase/Akt enhancer?
- Glial hemichannels and their involvement in aging and neurodegenerative diseases
- Diversity of presynaptic calcium channels displaying different synaptic properties
- α-Synuclein phosphorylation as a therapeutic target in Parkinson’s disease
- A historical justification for and retrospective analysis of the systematic application of light therapy in Parkinson’s disease
- Masthead
- Masthead
