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Choline metabolism as a basis for the selective vulnerability of cholinergic neuronsThe unique propensity of cholinergic neurons to use choline for two purposes--ACh and membrane phosphatidylcholine synthesis--may contribute to their selective vulnerability in Alzheimer's disease and other cholinergic neurodegenerative disorders. When physiologically active, the neurons use free choline taken from the 'reservoir' in membrane phosphatidylcholine to synthesize ACh; this can lead to an actual decrease in the quantity of membrane per cell. Alzheimer's disease (but not Down's syndrome, or other neurodegenerative disorders) is associated with characteristic neurochemical lesions involving choline and ethanolamine: brain levels of these compounds are diminished, while those of glycerophosphocholine and glycerophosphoethanolamine (breakdown products of their respective membrane phosphatides) are increased, both in cholinergic and noncholinergic brain regions. Perhaps this metabolic disturbance and the tendency of cholinergic neurons to 'export' choline--in the form of ACh--underlie the selective vulnerability of the neurons. Resulting changes in membrane composition could abnormally expose intramembraneous proteins such as amyloid precursor protein to proteases.
Document ID
20050000739
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Wurtman, R. J.
(Massachusetts Institute of Technology Cambridge 02139)
Date Acquired
August 22, 2013
Publication Date
April 1, 1992
Publication Information
Publication: Trends in neurosciences
Volume: 15
Issue: 4
ISSN: 0166-2236
Subject Category
Life Sciences (General)
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Regulatory Physiology
Review
Review, Tutorial
Non-NASA Center

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