Cyclin-dependent kinase 5, Munc18a and Munc18-interacting protein 1/X11α protein up-regulation in Alzheimer’s disease

Besides formation of neurofibrillary tangles and neuron loss, the Alzheimer’s disease brain is characterized by neuritic plaques consisting of β-amyloid peptide deposits and impaired neurotransmission. The proteins Munc18a, Munc18-interacting protein 1 and Munc18-interacting protein 2 mediate exocyt...

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Vydané v:	Neuroscience Ročník 138; číslo 2; s. 511 - 522
Hlavní autori:	Jacobs, E.H., Williams, R.J., Francis, P.T.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Oxford Elsevier Ltd 2006 Elsevier
Predmet:	Biological and medical sciences Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Fundamental and applied biological sciences. Psychology Medical sciences Neurology neuron loss neurotransmission occipital cortex parietal cortex Tg2576 transgenic mice Vertebrates: nervous system and sense organs β-amyloid PBS APP SNAP25 NP neurotransmission AD SDS Mint parietal cortex PAGE occipital cortex Tg2576 transgenic mice Aβ Cdk5 MMSE PBST neuron loss NF-68 NFT WT β-amyloid BA Nervous system diseases Enzyme Alzheimer disease Transferases Rodentia Central nervous system Transgenic animal Cyclin Cerebral disorder Vertebrata Mammalia Mouse Kinase Cell death β Amyloid protein Occipital cortex Central nervous system disease Parietal cortex Degenerative disease Neurotransmission
ISSN:	0306-4522, 1873-7544
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Shrnutí:	Besides formation of neurofibrillary tangles and neuron loss, the Alzheimer’s disease brain is characterized by neuritic plaques consisting of β-amyloid peptide deposits and impaired neurotransmission. The proteins Munc18a, Munc18-interacting protein 1 and Munc18-interacting protein 2 mediate exocytosis and decrease β-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 β-amyloid precursor protein with the Swedish mutation known to lead to familial Alzheimer’s disease, which have substantial levels of β-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 β-amyloid peptide levels early during the progression of Alzheimer’s disease.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0306-4522 1873-7544
DOI:	10.1016/j.neuroscience.2005.11.017