| Autor: |
Braithwaite, Steven P., Stock, Jeffry B., Mouradian, M. Maral |
| Zdroj: |
Reviews in the Neurosciences; April 2012, Vol. 23 Issue: 2 p191-198, 8p |
| Abstrakt: |
AbstractPhosphorylation 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. |
| Databáze: |
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