Abstract
The genes encoding presenilin 1 (PS-1) on chromosome 14 and presenilin 2 (PS-2) on chromosome 1 have been identified as major causal genes for early onset familial Alzheimer’s disease (FAD) (Sherington et al. 1995; Levy-Lahad et al., 1995). Genetic studies showed that early onset FAD linked to chromosomes 14 and 1 is caused by mis-sence mutations in PS-1 and PS-2 (Sherington et al. 1995; Levy-Lahad et ai., 1995). Patients with this form of FAD revealed increased levels of highly amyloidogenic species of amyloid beta protein (Aβ1–42 and Aβ1–43) in plasma and cerebral amyloid depositions (Scheuner et al. 1996; Mann et al. 1996). In addition, presenilins were shown to form stable complexes with amyloid precursor protein (APP) (Weidemann et al. 1997). Although mechanism of Aβ 1–42 and Aβ 1–43 accumulation in FAD is not clear the results above suggest that PS-1 and PS-2 are directly or indirectly involved in the APP metabolism and amyloid formation. Recently PS-2 gene was shown to contribute to apoptosis induced by trophic factor withdrawal, β-amyloid, and T cell receptor-induced apoptosis (Wolozin et al. 1996; Vito et al., 1996). Light and electron microscopy studies suggest predominant localization of PS-1 to the nuclear membrane, endoplasmic reticulum (ER)-Golgi compartments and coated transport vesicles (Cook et al., 1996; Kovacset al., 1996; Lahet al., 1997).
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Schwarzman, A., Tsiper, M., Vitek, M., George-Hyslop, P.S., Goldgaber, D. (1998). Identification of Peptides Binding to Presenilin 1 by Screening of Random Peptide Display Libraries. In: Fisher, A., Hanin, I., Yoshida, M. (eds) Progress in Alzheimer’s and Parkinson’s Diseases. Advances in Behavioral Biology, vol 49. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5337-3_20
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DOI: https://doi.org/10.1007/978-1-4615-5337-3_20
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