Aβ 1-40 enhances the proliferation of human diploid fibroblasts.

There is a vast literature on the role of beta amyloid (Aβ) peptides in the pathogenesis of Alzheimer's disease. However, there is a paucity of research on the potential physiological functions of these evolutionarily conserved products of the Aβ precursor protein. Based on previous studies in neuroblastoma cells, we hypothesized that Aβ may contribute to the proliferation of somatic cells.

DNA damage accumulation and TRF2 degradation in atypical Werner syndrome fibroblasts with LMNA mutations.

Segmental progeroid syndromes are groups of disorders with multiple features suggestive of accelerated aging. One subset of adult-onset progeroid syndromes, referred to as atypical Werner syndrome, is caused by mutations in the LMNA gene, which encodes a class of nuclear intermediate filaments, lamin A/C. We previously described rapid telomere attrition and accelerated replicative senescence in cultured fibroblasts overexpressing mutant lamin A.

Age-related retention of fiber cell nuclei and nuclear fragments in the lens cortices of multiple species.

Purpose: To determine the differences between species in the retention of lens fiber cell nuclei and nuclear fragments in the aging lens cortex and the relationship of nuclear retention to lens opacity. For this purpose old human, monkey, dog, and rat lenses were compared to those of three strains of mouse. We also investigated possible mechanisms leading to nuclear retention.

X-ray induced cataract is preceded by LEC loss, and coincident with accumulation of cortical DNA, and ROS; similarities with age-related cataracts.

Purpose: To compare age-related cataractous (ARC) changes in unirradiated mice lenses to those induced by head-only X-irradiation of 3 month-old mice.

Methods: lens epithelial cells (LECs) as well as partially degraded cortical DNA were visualized in fixed sections using 4',6-diamidino-2-phenylindole (DAPI) staining, and in fresh lenses using the vital stain Hoechst 33342. reactive oxygen species (ROS) activity was also visualized directly in fresh lenses using the vital dye Dihydrorhodamine (DHR).

Structural and functional characterization of a novel FE65 protein product up-regulated in cognitively impaired FE65 knockout mice.

FE65 is a multi-modular adaptor protein that binds the cytoplasmic tail of the beta-amyloid precursor protein (APP). Genetic evidence suggests that APP is intimately involved in the pathogenesis of dementias of the Alzheimer type, neurodegenerative disorders that affect multiple cognitive domains, including learning and memory. Evidence from p97FE65-specific knockout mice (lacking the 97 kDa full-length FE65 protein, p97FE65) suggests an important role for FE65 in learning and memory.

Localizations of endogenous APP/APP-proteolytic products are consistent with microtubular transport.

Dementia of the Alzheimer type (DAT) is associated with the accumulation of beta-amyloid (A beta) peptides derived from beta-amyloid precursor protein (APP). Goldstein and coworkers have suggested that APP acts as a cargo receptor connecting post-Golgi vesicles and motor proteins. Sisodia and colleagues have suggested that APP is a passive passenger within the vesicles.

Endoproteolytic cleavage of FE65 converts the adaptor protein to a potent suppressor of the sAPPalpha pathway in primates.

Adaptor protein FE65 (APBB1) specifically binds to the intracellular tail of the type I transmembrane protein, beta-amyloid precursor protein (APP). The formation of this complex may be important for modulation of the processing and function of APP. APP is proteolytically cleaved at multiple sites.