Sorting Out Presenilins in Alzheimer’s Disease

γ-secretases: from cell biology to therapeutic strategies

Presenilins form the catalytic part of the γ-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 β-amyloid (Aβ) peptide in Alzheimer’s disease and are therefore thought to be important drug targets for this disorder. ...

Neurobiology of Disease Role of Presenilins in Neuronal Calcium Homeostasis

Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disorder. Familial AD (FAD) mutations in presenilins have been linked to calcium (Ca 2 ) signaling abnormalities. To explain these results, we previously proposed that presenilins function as endoplasmic reticulum (ER) passive Ca 2 leak channels. To directly investigate the role of presenilins in neuronal ER Ca 2 homeo...

Op-brai150131 2005..2019

Endophilin-B1, also known as Bax-interacting factor 1 (Bif-1, and encoded by SH3GLB1), is a multifunctional protein involved in apoptosis, autophagy and mitochondrial function. We recently described a unique neuroprotective role for neuron-specific alternatively spliced isoforms of endophilin-B1. To examine whether endophilin-B1-mediated neuroprotection could be a novel therapeutic target for A...

Mutations in the presenilin 1 (PS1) gene on chromosome 14 account for a large proportion of the early onset familial cases of Alzheimer’s disease

Sex effect on presenilins expression in post-natal rat brain

Presenilin 1 and presenilin 2 are widely expressed during brain development. Several mutations in these proteins have been associated with autosomal-dominant inherited forms of Alzheimer disease. Their expression is regulated by various cellular and extracellular factors, which change with age and sex. Both age and sex are key risk factors for Alzheimer’s disease, but the issue of whether the e...