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The molecular link between beta- and gamma-secretase activity on the amyloid beta precursor protein.
Cell Mol Life Sci. 2007 Sep; 64(17):2211-8.CM

Abstract

Alzheimer's disease (AD) is characterized by an accumulation in the brain of amyloid beta peptides (Abeta). The production of Abeta requires two sequential cleavages induced by beta- and gamma-secretases on the beta-amyloid precursor protein (APP). Altered activity of these secretases is involved in the pathogenesis of AD. The expression and activity of beta-secretase (BACE1) is augmented in the brain in late-onset sporadic AD. Mutant presenilin 1 (PS1), the major genetic defect of early-onset familial AD (FAD), alters the activity of gamma-secretase, leading to increased production of Abeta42. Here we review the role of oxidative stress as a molecular link between the beta- and the gamma-secretase activities, and provide a mechanistic explanation of the pathogenesis of sporadic late-onset AD. We also discuss evidence for a role of the same mechanism in the pathogenesis of familial AD carrying PS1 mutations.

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Authors+Show Affiliations

Tabaton M
Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Via De Toni 2, 16132, Genoa, Italy. mtabaton@neurologia.unige.it
Tamagno E
No affiliation info available

MeSH

Alzheimer DiseaseAmyloid Precursor Protein SecretasesAmyloid beta-Protein PrecursorAspartic Acid EndopeptidasesHumansOxidative StressPresenilins

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

17604999

Citation

Tabaton, M, and E Tamagno. "The Molecular Link Between Beta- and Gamma-secretase Activity On the Amyloid Beta Precursor Protein." Cellular and Molecular Life Sciences : CMLS, vol. 64, no. 17, 2007, pp. 2211-8.
Tabaton M, Tamagno E. The molecular link between beta- and gamma-secretase activity on the amyloid beta precursor protein. Cell Mol Life Sci. 2007;64(17):2211-8.
Tabaton, M., & Tamagno, E. (2007). The molecular link between beta- and gamma-secretase activity on the amyloid beta precursor protein. Cellular and Molecular Life Sciences : CMLS, 64(17), 2211-8.
Tabaton M, Tamagno E. The Molecular Link Between Beta- and Gamma-secretase Activity On the Amyloid Beta Precursor Protein. Cell Mol Life Sci. 2007;64(17):2211-8. PubMed PMID: 17604999.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The molecular link between beta- and gamma-secretase activity on the amyloid beta precursor protein. AU - Tabaton,M, AU - Tamagno,E, PY - 2007/7/3/pubmed PY - 2007/11/10/medline PY - 2007/7/3/entrez SP - 2211 EP - 8 JF - Cellular and molecular life sciences : CMLS JO - Cell Mol Life Sci VL - 64 IS - 17 N2 - Alzheimer's disease (AD) is characterized by an accumulation in the brain of amyloid beta peptides (Abeta). The production of Abeta requires two sequential cleavages induced by beta- and gamma-secretases on the beta-amyloid precursor protein (APP). Altered activity of these secretases is involved in the pathogenesis of AD. The expression and activity of beta-secretase (BACE1) is augmented in the brain in late-onset sporadic AD. Mutant presenilin 1 (PS1), the major genetic defect of early-onset familial AD (FAD), alters the activity of gamma-secretase, leading to increased production of Abeta42. Here we review the role of oxidative stress as a molecular link between the beta- and the gamma-secretase activities, and provide a mechanistic explanation of the pathogenesis of sporadic late-onset AD. We also discuss evidence for a role of the same mechanism in the pathogenesis of familial AD carrying PS1 mutations. SN - 1420-682X UR - https://www.unboundmedicine.com/medline/citation/17604999/The_molecular_link_between_beta__and_gamma_secretase_activity_on_the_amyloid_beta_precursor_protein_ L2 - https://doi.org/10.1007/s00018-007-7219-3 DB - PRIME DP - Unbound Medicine ER -