Presenilin enhancer-2 proteins

There may be several distinct PS complexes. Gu et al. (150) proposed the existence of at least three complexes (1) an approx. 150-kDa nicastrin-APHl (anterior pharynx defective 1 protein) complex (which is likely to be a precursor complex) (2) a stable and abundant intermediate complex of 440 kDa that contains APHl, PEN2 (presenilin enhancer 2), nicastrin, and PSl and (3) a high mass (>670-kDa) heteromeric complex (PS i-APHl-NCT-PEN2) associated with the highest y-secretase-specific activity (150) (see Fig. 10.3). 

Impairment of glucose metabolism is a major feature of Alzheimer s disease. Pan et al. (59) have examined the effect of benfotiamine on cognitive impairment and pathology in the amyloid precursor proteins/presenilin-1 transgenic mice, a mouse model of Alzheimer s disease. Chronic treatment with benfotiamine enhanced the spatial memory of the mice and also reduced both amyloid plaque numbers and phosphorylated tau levels in the cortical areas. Benfotiamine increased the phosphorylation level of glycogen synthase kinase-3a and 3P and reduced their enzyme activities, a newer aspect of the effect of benfotiamine. 

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