Alzheimer's Disease: Advances in Genetics, Molecular and - download pdf or read online
By Sangram S. Sisodia, Rudolph E. Tanzi
This publication examines each significant point of Alzheimer ailment – scientific, epidemiologic, structural, chemical, genetic, molecular, and healing. This variation contains improved assurance of the cellular-level exploration of comparable dementing problems, with in-depth presentation of prion illnesses, Pick's affliction, fronto-temporal issues, transgenic types, and biochemistry of presenilins. therapy of indicators with healing medicines is mentioned, in addition to results of and difficulties inherent in medical trials for advert. The large insurance of advert during this publication merits clinicians, educators, investigators, and healthiness administrators.
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Additional info for Alzheimer's Disease: Advances in Genetics, Molecular and Cellular Biology
2000). Interestingly, APLP2-/- /APLP1-/- and APP-/- /APLP2-/- double mutants, but not APP-/- /APLP1-/- animals, showed early postnatal lethality, indicating that members of the APP gene family are essential genes that exhibit partial overlapping functions. Curiously, the histopathological phenotype of the animals that displayed early lethality was rather bland by initial descriptions. Similarly, neurons cultured from these animals were unaltered in their basal growth rates or response to excitotoxicity.
Nevertheless, the intracellular organelles/transport vesicles where Aβ is generated in neurons are not fully characterized. Studies conducted in non-neuronal and neuroblastoma cell lines show that Aβ is mainly generated in TGN as APP is trafﬁcked through the secretory and recycling pathways (Figure 2). Attempts to address the role of endocytic APP trafﬁcking by expression of dominant-negative mutant of dynamin, an important component of the endocytic machinery, resulted in discrepant ﬁndings. This is not surprising, since overexpression of mutant dynamin causes pleiotropic effects on endocytic trafﬁcking of numerous proteins including APP secretases.
In cultured cells and tissues, NTF and CTF are the principal PS-related polypeptides that are observed, but low levels of full length PS 38 Tomoko Wakabayashi, Takeshi Iwatsubo and Bart De Strooper Figure 1. Transmembrane structure of presenilin. A. Eight transmembrane model of presenilin. Two putative active site aspartates in TM6 and TM7 are marked. The location of the endoproteolytic cleavage site by “presenilinase activity” within the large cytoplasmic loop is indicated. NTF: aminoterminal fragment, CTF: carboxyterminal fragment.
Alzheimer's Disease: Advances in Genetics, Molecular and Cellular Biology by Sangram S. Sisodia, Rudolph E. Tanzi