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Keeping Our Calcium in Balance to Maintain Our Balance.

Abstract：

:Calcium is a key signaling molecule and ion involved in a variety of diverse processes in our central nervous system (CNS) which include gene expression, synaptic transmission and plasticity, neuronal excitability and cell maintenance. Proper control of calcium signaling is not only vital for neuronal physiology but also cell survival. Mutations in fundamental channels, transporters and second messenger proteins involved in orchestrating the balance of our calcium homeostasis can lead to severe neurodegenerative disorders, such as Spinocerebellar (SCA) and Episodic (EA) ataxias. Hereditary ataxias make up a remarkably diverse group of neurological disorders clinically characterized by gait ataxia, nystagmus, dysarthria, trunk and limb ataxia and often atrophy of the cerebellum. The largest family of hereditary ataxias is SCAs which consists of a growing family of 42 members. A relatively smaller family of 8 members compose the EAs. The gene mutations responsible for half of the EA members and over 35 of the SCA subtypes have been identified, and several have been found to be responsible for cerebellar atrophy, abnormal intracellular calcium levels, dysregulation of Purkinje cell pacemaking, altered cerebellar synaptic transmission and/or ataxia in mouse models. Although the genetic diversity and affected cellular pathways of hereditary ataxias are broad, one common theme amongst these genes is their effects on maintaining calcium balance in primarily the cerebellum. There is emerging evidence that the pathogenesis of hereditary ataxias may be caused by imbalances in intracellular calcium due to genetic mutations in calcium-mediating proteins. In this review we will discuss the current evidence supporting the role of deranged calcium as the culprit to neurodegenerative diseases with a primary focus on SCAs and EAs.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Mark MD,Schwitalla JC,Groemmke M,Herlitze S

doi

10.1016/j.bbrc.2016.07.020

subject

Has Abstract

pub_date

2017-02-19 00:00:00

pages

1040-1050

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(16)31135-4

journal_volume

483

pub_type

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Keeping Our Calcium in Balance to Maintain Our Balance.