Presenilins form the catalytic part of the gamma-secretases, protein complexes 
that are responsible for the intramembranous cleavage of transmembrane proteins. 
The presenilins are involved in several biological functions, but are best known 
for their role in the generation of the beta-amyloid (Abeta) peptide in 
Alzheimer's disease and are therefore thought to be important drug targets for 
this disorder. Mutations in the presenilin genes cause early-onset familial 
Alzheimer's disease, but mutation carriers have substantial phenotypic 
heterogeneity. Recent evidence implicating presenilin mutations in 
non-Alzheimer's dementias, including frontotemporal dementia and Lewy body 
dementia, warrants further investigation. An increased understanding of the 
diversity of the molecular cell biology of the gamma-secretase complex and the 
effects of clinical mutations in the presenilin genes might help pave the way 
for improved development of drugs that are designed to target gamma-secretase 
enzymatic activity in Alzheimer's disease and potentially in other neurological 
diseases.