Inhibitors beta-amyloid-induced toxicity by modulating the Akt signaling pathway.
The Akt signaling pathway plays a crucial role in neuronal survival, leading to inhibition of apoptosis. Many stimulants including neurotrophins are reported to activate this pathway in preclinical studies; however, there are no drugs for neurodegenerative diseases adopting such a concept on the market so far. Among neurodegenerative diseases, Alzheimer's disease is the most common and characterized by senile plaques and neurofibrillary tangles, which consist of beta-amyloid and hyperphosphorylated tau, respectively. Recent studies suggest that activation of Akt inhibits toxicity of beta-amyloid and formation of neurofibrillary tangles, leading to protection of neurons against apoptosis. This review discusses the possibility of treatment of Alzheimer's disease by activating the Akt signaling pathway.
Nakagami
Yasuhiro
Y
Biological Research Laboratories, Sankyo Co., Ltd., Tokyo 140-8710, Japan. yasuhiro@sankyo.co.jp
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt
D016229:Amyloid beta-Peptides; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494918:AKT1 protein, human