Neuronal death in Alzheimer's disease and therapeutic opportunities

被引:85
作者
Donev, Rossen [1 ]
Kolev, Martin [1 ]
Millet, Bruno [2 ]
Thome, Johannes [3 ]
机构
[1] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff, S Glam, Wales
[2] Univ Rennes, Ctr Hosp Guillaume Regnier, Serv Hosp Univ Psychiat Adulte, Rennes, France
[3] Swansea Univ, Sch Med, Inst Life Sci, Acad Unit Psychiat, Singleton Pk, Swansea SA2 8PP, W Glam, Wales
基金
英国医学研究理事会;
关键词
Alzheimer's disease; neuronal death; neurodegeneration; neurotoxicity; neuroprotection; amyloid plaques; HERPES-SIMPLEX-VIRUS; AMYLOID-BETA-PROTEIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GAMMA-SECRETASE INHIBITOR; COMPLEMENT COMPONENT C1Q; LONG-TERM POTENTIATION; A-BETA; PRECURSOR PROTEIN; IN-VIVO; COBRA VENOM;
D O I
10.1111/j.1582-4934.2009.00889.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Introduction Origin of the disease and mechanisms for neuronal death in AD Inflammatory reaction A beta-induced neurotoxicity Complement-mediated neurodegeneration Oxidative and nitrosylative damage Proteasome inhibitor-induced neurotoxicity Cholesterol-induced neurotoxicity Viral infections Interrelationship between different aetiopathogenic theories of AD Treatment approaches Drugs which modify AD symptoms Cholinergic treatment Antiglutamic treatment beta- and gamma-secretase inhibitors Drugs which potentially prevent and modify AD symptoms Vitamins and antioxidants Non-steroidal anti-inflammatory drugs Oestrogen replacement therapy Inhibitors of complement-mediated degeneration Cobra venom factor (CVF) Heparin and other polyionic agents Other small molecule inhibitors Recombinant protein inhibitors Anti-amyloid therapy ('vaccination') Targeting proteasome inhibition Neuropeptide mixture (Cerebrolysin) Conclusions Alzheimer's disease (AD) is an age-related neurodegenerative disease that affects approximately 24 million people worldwide. A number of different risk factors have been implicated in AD; however, neuritic (amyloid) plaques are considered as one of the defining risk factors and pathological hallmarks of the disease. In the past decade, enormous efforts have been devoted to understand the genetics and molecular pathogenesis leading to neuronal death in AD, which has been transferred into extensive experimental approaches aimed at reversing disease progression. Modern medicine is facing an increasing number of treatments available for vascular and neurodegenerative brain diseases, but no causal or neuroprotective treatment has yet been established. Almost all neurological conditions are characterized by progressive neuronal dysfunction, which, regardless of the pathogenetic mechanism, finally leads to neuronal death. The particular emphasis of this review is on risk factors and mechanisms resulting in neuronal loss in AD and current and prospective opportunities for therapeutic interventions. This review discusses these issues with a view to inspiring the development of new agents that could be useful for the treatment of AD.
引用
收藏
页码:4329 / 4348
页数:20
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