Galanin in Alzheimer's disease: Neuroinhibitory or neuroprotective?

Document Type

Article

Abstract

Galanin (GAL) and GAL receptors (GALRs) are overexpressed in degenerating brain regions associated with cognitive decline in Alzheimer's disease (AD). The functional consequences of GAL plasticity in AD are unclear. GAL inhibits cholinergic transmission in the hippocampus and impairs spatial memory in rodent models, suggesting GAL overexpression exacerbates cognitive impairment in AD. By contrast, gene expression profiling of individual cholinergic basal forebrain (CBF) neurons aspirated from AD tissue revealed that GAL hyperinnervation positively regulatesmRNAs that promote CBF neuronal function and survival. GAL also exerts neuroprotective effects in rodent models of neurotoxicity. These data support the growing concept that GAL overexpression preserves CBF neuron function which in turn may slow the onset of AD symptoms. Further elucidation of GAL activity in selectively vulnerable brain regions will help gauge the therapeutic potential of GALR ligands for the treatment of AD. (Part of a Multi-author Review). © 2008 Birkhaueser.

Keywords

Alzheimer's disease, Cholinergic basal forebrain, Galanin, Hippocampus, Plasticity

Publication Date

6-1-2008

Publication Title

Cellular and Molecular Life Sciences

ISSN

1420682X

E-ISSN

15691632

Volume

65

Issue

12

First Page

1842

Last Page

1853

PubMed ID

18500641

Digital Object Identifier (DOI)

10.1007/s00018-008-8159-2

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