6533b82ffe1ef96bd1294efb

RESEARCH PRODUCT

Implications of alpha- and beta-secretase expression and function in Alzheimer's disease

Kristina EndresSven Reinhardt

subject

PathogenesisbiologyADAM10biology.proteinAmyloid precursor proteinAlpha (ethology)DiseaseAmyloid precursor protein secretaseNeuroscienceFunction (biology)Biochemistry of Alzheimer's disease

description

Abstract There has been intense debate in the field about the extent to which processing of the amyloid precursor protein contributes to pathogenesis of Alzheimer's disease. Early publications succeeding in the identification of the main component of senile plaques—the amyloid-beta (A-beta) peptide—strictly argued for a constitutive contribution of A-beta to disease initiation and progression. This led to development of the amyloid hypothesis, which in recent years was attacked for the lack of success of clinical studies based on the respective assumption. There is evidence that the hypothesis must be revisited, but accumulation of A-beta along with aging might still be the best explanation for disease development. Therefore, it is important to understand mechanisms that balance synthesis, transport, and degradation of A-beta. The main enzyme laying groundwork for A-beta production is the beta-secretase BACE-1. Its enzymatic opponent is represented by the alpha-secretase ADAM10 in neurons. ADAM10 prevents formation of A-beta by cleaving within the peptide's stretch. In this chapter we focus on knowledge about balance of the two enzymes, alpha- and beta-secretase, in aging and disease.

yearjournalcountryeditionlanguage
2020-01-01
https://doi.org/10.1016/b978-0-12-815868-5.00016-5