Aberrant Expression of RCAN1 in Alzheimer’s Pathogenesis: A New Molecular Mechanism and a Novel Drug Target

Apr 23, 2014Molecular neurobiology

Unusual RCAN1 Levels in Alzheimer's Disease: A Possible New Cause and Drug Target

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Abstract

Dysregulation of regulator of calcineurin 1 (RCAN1) is associated with neuronal loss and neurofibrillary tangle formation in Alzheimer's disease.

Patients with Alzheimer's disease exhibit neuritic plaques, neurofibrillary tangles, and neuronal loss.
Aberrant expression of RCAN1 may facilitate neuronal cell death and contribute to Tau hyperphosphorylation.
RCAN1 dysregulation could promote synaptic impairments and influence the development of neurofibrillary tangles.
Risk factors for Alzheimer's disease may induce changes in RCAN1 expression, impacting neuronal health.
The review discusses potential mechanisms by which RCAN1 affects amyloid precursor protein processing and amyloid-beta generation.

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AD, a devastating neurodegenerative disorder, is the most common cause of dementia in the elderly. Patients with AD are characterized by three hallmarks of neuropathology including neuritic plaque deposition, neurofibrillary tangle formation, and neuronal loss. Growing evidences indicate that dysregulation of regulator of calcineurin 1 (RCAN1) plays an important role in the pathogenesis of AD. Aberrant RCAN1 expression facilitates neuronal apoptosis and Tau hyperphosphorylation, leading to neuronal loss and neurofibrillary tangle formation. This review aims to describe the recent advances of the regulation of RCAN1 expression and its physiological functions. Moreover, the AD risk factors-induced RCAN1 dysregulation and its role in promoting neuronal loss, synaptic impairments and neurofibrillary tangle formation are summarized. Furthermore, we provide an outlook into the effects of RCAN1 dysregulation on APP processing, Aβ generation and neuritic plaque formation, and the possible underlying mechanisms, as well as the potential of targeting RCAN1 as a new therapeutic approach.

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Aberrant Expression of RCAN1 in Alzheimer’s Pathogenesis: A New Molecular Mechanism and a Novel Drug Target

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