Research progress of apoptosis pathways and caspases as therapeutic targets involved in Alzheimer′s disease
10.3969/j.issn.1001-1978.2015.11.005
- VernacularTitle:凋亡通路及caspases在阿尔茨海默病中作为治疗靶点的研究
- Author:
Wenbao WU
;
Qinghong KONG
;
Xiangxu KAN
;
Guanlin WANG
;
Kwenjen CHANG
- Publication Type:Journal Article
- Keywords:
caspase;
Alzheimer′s disease;
tau;
Aβ;
apoptosis;
therapeutic targets;
drug therapy
- From:
Chinese Pharmacological Bulletin
2015;(11):1496-1501
- CountryChina
- Language:Chinese
-
Abstract:
Alzheimer′s disease ( AD) is a type of neurodegener-ative disease. Recent studies indicate that neuronal degeneration and loss triggered by tau, APP and Aβare the probable risks for AD. Neurofibrillary tangles are formed after tau truncated by ac-tivated caspases and subsequently induced tau aggregates, which causes neuronal degeneration and loss. In addition, caspases are crucial components in the biological functioning in the apoptosis pathways. Apoptosis pathway involves activation of upstream ini-tiator caspase-8 and downstream executor caspase-3/-6/-7. After the actions of β- and γ-secretase, APP transforms into sAPPβand Aβ40/42 . Aggregated Aβ42 can activate apoptosis pathway through DR4/5 interaction. C-APP is truncated into C31 frag-ments by caspases and cell apoptosis is facilitated. N-APP, a product of sAPPβhydrolysis, can promote the abnormal develop-ment of neurons mediated by DR6. Caspase activates γ-secre-tase-activating protein to regulate activity ofγ-secretase, and the production of C31 and Aβ40/42 , which, then, causes the occur-rence of AD. This brief review summarizes the specific roles of caspases and the concerning apoptosis pathways on the mecha-nisms of neuronal degeneration and loss, and how they impact the occurrence of AD in the hope of uncovering additional poten-tial therapeutic targets that can be employed in drug development and clinical therapy for AD.
