Addressing Alzheimer's Disease Tangles: From NAP to AL-108

被引：78

作者：

Gozes, Illana ^{[1
,2
]}

Stewart, Alistair ^{[2
]}

Morimoto, Bruce ^{[2
]}

Fox, Anthony ^{[2
]}

Sutherland, Karole ^{[2
]}

Schmechel, Donald ^{[3
]}

机构：

[1] Tel Aviv Univ, Sackler Fac Med,Adams Super Ctr Brain Studies, Dept Human Mol Genet & Biochem,Lily & Avraham Gil, Elton Lab Neuroendocrinol,Inst Funct Brain Imagin, IL-69978 Tel Aviv, Israel

[2] Allon Therapeut Inc, Vancouver, BC V6B 2S2, Canada

[3] Duke Med Ctr, Durham, NC USA

来源：

CURRENT ALZHEIMER RESEARCH | 2009年 / 6卷 / 05期

关键词：

DEPENDENT NEUROPROTECTIVE PROTEIN; VASOACTIVE-INTESTINAL-PEPTIDE; TRANSGENIC MOUSE MODEL; HEAD-INJURY; A-BETA; POLY(ADP-RIBOSE) POLYMERASE; TAU-HYPERPHOSPHORYLATION; POLYADP-RIBOSYLATION; NEUROTROPHIC FACTOR; ADNP;

D O I：

10.2174/156720509789207895

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

AL-108 is the intranasal formulation of NAP (a peptide of eight amino acids, NAPVSIPQ). Phase IIa clinical results have recently shown that AL-108 has a positive impact on memory function in patients with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer's disease (AD). The clinical development of AL-108 has been based on extensive studies showing pre-clinical efficacy for NAP. NAP has demonstrated potent neuroprotective activity in vitro and in vivo. Its mechanism of action is thought to center on the modulation of microtubule stability in the face of outside damage. Such an effect on structures of such central importance in a broad range of cellular functions is thought to explain NAP's activity in wide ranging models of cellular damage and neurodegeneration. The following article reviews NAP's discovery and pharmacological characterization that has led to clinical development of a novel tangle-directed drug candidate.

引用

页码：455 / 460

页数：6

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