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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

TRPC Channels and their Implications for Neurological Diseases

Author(s): Senthil Selvaraj, Yuyang Sun and Brij B. Singh

Volume 9, Issue 1, 2010

Page: [94 - 104] Pages: 11

DOI: 10.2174/187152710790966650

Price: $65

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Abstract

Calcium is an essential intracellular messenger and serves critical cellular functions in both excitable and non-excitable cells. Most of the physiological functions in these cells are uniquely regulated by changes in cytosolic Ca2+ levels ([Ca2+]i), which are achieved via various mechanisms. One of these mechanism(s) is activated by the release of Ca2+ from the endoplasmic reticulum (ER), followed by Ca2+ influx across the plasma membrane (PM). Activation of PM Ca2+ channels is essential for not only refilling of the ER Ca2+ stores, but is also critical for maintaining [Ca2+]i that regulates biological functions, such as neurosecretion, sensation, long term potentiation, synaptic plasticity, gene regulation, as well as cellular growth and differentiation. Alterations in Ca2+ homeostasis have been suggested in the onset/progression of neurological diseases, such as Parkinsons, Alzheimers, bipolar disorder, and Huntingtons diseases. Available data on transient receptor potential conical (TRPC) protein indicate that these proteins initiate Ca2+ entry pathways and are essential in maintaining cytosolic, ER, and mitochondrial Ca2+ levels. A number of biological functions have been assigned to these TRPC proteins. Silencing of TRPC1 and TRPC3 has been shown to inhibit neuronal proliferation and loss of TRPC1 is implicated in neurodegeneration. Thus, TRPC channels not only contribute towards normal physiological processes, but are also implicated in several human pathological conditions. Overall, it is suggested that these channels could be used as potential therapeutic targets for many of these neurological diseases. Thus, in this review we have focused on the functional implication of TRPC channels in neuronal cells along with the elucidation of their role in neurodegeneration.


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