Cyclin-dependent kinase 5, Munc18a and Munc18-interacting protein 1/X11alpha protein up-regulation in Alzheimer's disease.

Abstract:

:Besides formation of neurofibrillary tangles and neuron loss, the Alzheimer's disease brain is characterized by neuritic plaques consisting of beta-amyloid peptide deposits and impaired neurotransmission. The proteins Munc18a, Munc18-interacting protein 1 and Munc18-interacting protein 2 mediate exocytosis and decrease beta-amyloid peptide formation. Cyclin-dependent kinase 5 and its activator p35 disrupt Munc18a-syntaxin 1 binding, thereby promoting synaptic vesicle fusion during exocytosis. We investigated protein levels of the signaling pathway: p35, cyclin-dependent kinase 5, Munc18a, syntaxin 1A and 1B, Munc18-interacting protein 1 and Munc18-interacting protein 2 in Alzheimer's disease cortex and found that this pathway was up-regulated in the Alzheimer's disease parietal and occipital cortex. In the cortex of transgenic Tg2576 mice over-expressing human beta-amyloid precursor protein with the Swedish mutation known to lead to familial Alzheimer's disease, which have substantial levels of beta-amyloid peptide but lack neurofibrillary tangles and neuron loss, no alterations of protein levels were detected. These data suggest that the pathway is enhanced in dying or surviving neurons and might serve a protective role by compensating for decreased neurotransmission and decreasing beta-amyloid peptide levels early during the progression of Alzheimer's disease.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Jacobs EH,Williams RJ,Francis PT

doi

10.1016/j.neuroscience.2005.11.017

keywords:

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

511-22

issue

2

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(05)01303-5

journal_volume

138

pub_type

杂志文章