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Proteolytic processing of the Alzheimer's disease amyloid precursor protein in brain and platelets.
J Neurosci Res. 2003 Nov 01; 74(3):386-92.JN

Abstract

Proteolytic processing of the amyloid precursor protein by beta -and gamma-secretases results in the production of Alzheimer's disease (AD) Abeta amyloid peptides. Modulation of secretase activity is being investigated as a potential therapeutic approach. Recent studies with human brain have revealed that the beta-secretase protein, BACE, is increased in cortex of AD patients. Analysis of betaCTF (or C99), the amyloid precursor protein (APP) product of BACE cleavage that is the direct precursor to Abeta, shows it is also elevated in AD, underlying the importance of beta-secretase cleavage in AD pathogenesis. The C-terminal product of gamma-secretase cleavage of APP, epsilonCTF (or AICD), is enriched in human brain cortical nuclear fractions, a subcellular distribution appropriate for a putative involvement of APP cytosolic domain in signal transduction. Analysis of AD cortex samples, particularly that of a carrier of a familial APP mutation, suggests that processing of APP transmembrane domain generates an alternative CTF product. All these particularities observed in the AD brain demonstrate that APP processing is altered in AD. The transgenic mouse model Tg2576 seems to be a promising laboratory tool to test potential modulators of Abeta formation. Indeed, C-terminal products of alpha-, beta-, and gamma-secretase cleavage are readily detectable in the brain of these transgenic mice. Finally, the finding of the same secretase products in platelets and neurons make platelets a potentially useful and easily accessible clinical tool to monitor effects of novel therapies based on inhibition of beta- or gamma-secretase.

Authors+Show Affiliations

Department of Pathology, University of Melbourne, Parkville, Australia. gmevin@unimelb.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

14598315

Citation

Evin, Geneviève, et al. "Proteolytic Processing of the Alzheimer's Disease Amyloid Precursor Protein in Brain and Platelets." Journal of Neuroscience Research, vol. 74, no. 3, 2003, pp. 386-92.
Evin G, Zhu A, Holsinger RM, et al. Proteolytic processing of the Alzheimer's disease amyloid precursor protein in brain and platelets. J Neurosci Res. 2003;74(3):386-92.
Evin, G., Zhu, A., Holsinger, R. M., Masters, C. L., & Li, Q. X. (2003). Proteolytic processing of the Alzheimer's disease amyloid precursor protein in brain and platelets. Journal of Neuroscience Research, 74(3), 386-92.
Evin G, et al. Proteolytic Processing of the Alzheimer's Disease Amyloid Precursor Protein in Brain and Platelets. J Neurosci Res. 2003 Nov 1;74(3):386-92. PubMed PMID: 14598315.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Proteolytic processing of the Alzheimer's disease amyloid precursor protein in brain and platelets. AU - Evin,Geneviève, AU - Zhu,Aiqin, AU - Holsinger,R M Damian, AU - Masters,Colin L, AU - Li,Qiao-Xin, PY - 2003/11/5/pubmed PY - 2003/12/20/medline PY - 2003/11/5/entrez SP - 386 EP - 92 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 74 IS - 3 N2 - Proteolytic processing of the amyloid precursor protein by beta -and gamma-secretases results in the production of Alzheimer's disease (AD) Abeta amyloid peptides. Modulation of secretase activity is being investigated as a potential therapeutic approach. Recent studies with human brain have revealed that the beta-secretase protein, BACE, is increased in cortex of AD patients. Analysis of betaCTF (or C99), the amyloid precursor protein (APP) product of BACE cleavage that is the direct precursor to Abeta, shows it is also elevated in AD, underlying the importance of beta-secretase cleavage in AD pathogenesis. The C-terminal product of gamma-secretase cleavage of APP, epsilonCTF (or AICD), is enriched in human brain cortical nuclear fractions, a subcellular distribution appropriate for a putative involvement of APP cytosolic domain in signal transduction. Analysis of AD cortex samples, particularly that of a carrier of a familial APP mutation, suggests that processing of APP transmembrane domain generates an alternative CTF product. All these particularities observed in the AD brain demonstrate that APP processing is altered in AD. The transgenic mouse model Tg2576 seems to be a promising laboratory tool to test potential modulators of Abeta formation. Indeed, C-terminal products of alpha-, beta-, and gamma-secretase cleavage are readily detectable in the brain of these transgenic mice. Finally, the finding of the same secretase products in platelets and neurons make platelets a potentially useful and easily accessible clinical tool to monitor effects of novel therapies based on inhibition of beta- or gamma-secretase. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/14598315/Proteolytic_processing_of_the_Alzheimer's_disease_amyloid_precursor_protein_in_brain_and_platelets_ L2 - https://doi.org/10.1002/jnr.10745 DB - PRIME DP - Unbound Medicine ER -