The role of APP proteolytic processing in lipid metabolism

Amyloid plaques in brains are one of the major pathological hallmarks of Alzheimer’s disease (AD). These plaques are mainly formed by aggregated Aβ, generated by proteolytic cleavage of the amyloid precursor protein (APP). Therefore, APP processing and Aβ production have been one of the central scop...

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Bibliographic Details
Published in:Experimental brain research 2012-04, Vol.217 (3-4), p.365-375
Main Authors: Grimm, Marcus O. W., Rothhaar, Tatjana L., Hartmann, Tobias
Format: Article
Language:English
Subjects:
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Alzheimer's disease
Amyloid beta-protein
Amyloid beta-Protein Precursor - physiology
Amyloid precursor protein
Animal models
Animals
beta -Amyloid
Biomedical and Life Sciences
Biomedicine
Brain
Cholesterol
Development and progression
Enzymes
Genetic aspects
Homeostasis
Humans
Lipid metabolism
Lipid Metabolism - physiology
Lipids
Metabolism
Neurodegenerative diseases
Neurology
Neurosciences
Peptides
Physiological aspects
Physiology
Plaques
Protein Processing, Post-Translational - physiology
Proteins
Proteolysis
Review
Reviews
Sphingolipids
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Summary:Amyloid plaques in brains are one of the major pathological hallmarks of Alzheimer’s disease (AD). These plaques are mainly formed by aggregated Aβ, generated by proteolytic cleavage of the amyloid precursor protein (APP). Therefore, APP processing and Aβ production have been one of the central scopes in AD research in the past. Now, accumulating evidence suggests that besides its pathological impact, APP and its cleavage products also contribute to physiological functions. Proteolytic cleavage of APP is tightly regulated, and several lipids such as cholesterol and sphingolipids have been shown to influence APP processing and Aβ generation. In turn, Aβ as well as other APP cleavage products plays an essential role in regulating lipid homeostasis arguing for complex regulatory cycles in which lipids control APP processing and vice versa. This balanced regulation is disrupted under pathological conditions such as in AD. This article will review the physiological function of APP and its proteolytic products, especially Aβ and AICD, in regulating lipid homeostasis and which lipid species modulate APP processing. Furthermore, we summarize the alterations in lipid metabolism observed in AD patients and AD mouse models.
ISSN:0014-4819
1432-1106
DOI:10.1007/s00221-011-2975-6