Presenilins as therapeutic targets for the treatment of Alzheimer's disease

Todd E. Golde, Steven G Younkin

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Studies demonstrating that accumulation and aggregation of the amyloid β protein (Aβ) within the brain is likely to cause Alzheimer's disease (AD) have provided the rationale for therapeutic strategies aimed at influencing Aβ production, aggregation and clearance. γ-secretase catalyzes the final cleavage that releases the Aβ from its precursor; therefore, it is a potential therapeutic target for the treatment of AD. Recent data show that the polytopic membrane proteins presenilin 1 and presenilin 2 are either catalytic components or essential co-factors of a membrane-bound proteolytic complex that possesses γ-secretase activity. Although recent findings demonstrating that γ-secretase inhibitors bind directly to presenilins (PSs) further support a catalytic role for PSs in γ-secretase cleavage, additional studies are still needed to clarify the role of PSs in γ-secretase cleavage and the use of targeting PSs to reduce Aβ production.

Original languageEnglish (US)
Pages (from-to)264-269
Number of pages6
JournalTrends in Molecular Medicine
Volume7
Issue number6
DOIs
StatePublished - 2001

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Presenilins
Amyloid Precursor Protein Secretases
Alzheimer Disease
Presenilin-2
Presenilin-1
Therapeutics
Serum Amyloid A Protein
Membrane Proteins
Membranes
Brain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Presenilins as therapeutic targets for the treatment of Alzheimer's disease. / Golde, Todd E.; Younkin, Steven G.

In: Trends in Molecular Medicine, Vol. 7, No. 6, 2001, p. 264-269.

Research output: Contribution to journalArticle

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