Type 1 metabotropic glutamate receptor and its signaling molecules as therapeutic targets for the treatment of cerebellar disorders


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Abstract

HighlightsmGluR1 and its signaling in Purkinje cells are essential for cerebellar functions.Impaired mGluR1 signaling is found in many animal models of cerebellar ataxia.Pharmacological repair of aberrant mGluR1 signaling mitigates the animals' symptoms.mGluR1 signaling is a therapeutic target for the treatment of cerebellar disorders.Neurodegenerative diseases such as spinocerebellar ataxias and autoantibody-associated disorders of the central nervous system often affect the cerebellum, resulting in motor deficits. Recent studies have revealed that most of these disorders impair type 1 metabotropic glutamate receptor (mGluR1) and/or the closely associated signaling molecules in cerebellar Purkinje cell. Since the signaling pathway triggered by mGluR1 activation in Purkinje cell plays a pivotal role in coordinated movements and motor learning, pharmacological repair of aberrant mGluR1 signaling in Purkinje cell is critical for mitigation of cerebellar symptoms. Here we review recently identified pathophysiology underlying the neurodegenerative and autoimmune diseases affecting mGluR1 signaling in Purkinje cell and possible therapeutic interventions.

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