Cell Death Targets and Potential Modulators in Alzheimers Disease

Rui      E. Castro; Maria      M.M. Santos; Paulo      M.C. Gloria; Carlos      J.A. Ribeiro; Duarte      M.S. Ferreira; Joana      M. Xavier; Rui      Moreira; Cecilia      M.P. Rodrigues

Abstract

Apoptosis is now recognized as a normal feature in the development of the nervous system and may also play a role in neurodegenerative disorders, such as Alzheimers disease. Cell surface receptors, caspases, mitochondrial factors or p53 participate in the modulation and execution of cell death. Therefore, the ability to understand and manipulate the cell death machinery is an obvious goal of medical research. Potential therapeutic approaches to modulate disease by regulating apoptosis are being tested, and include the traditional use of small molecules to target specific players in the apoptosis cascade. As our understanding of apoptosis increases, further opportunities will arise for more specific therapies that will result in improved efficacy. This review focuses on molecular mechanisms of apoptosis in Alzheimers disease and highlights the potential use of small molecule modulators to treat neurodegenerative disorders.

Keywords: Alzheimer's disease, Bcl-2 family, Caspases, Death receptors, Mitochondria, p53, Small molecules, Homeostasis, Apoptosis, Reactive oxygen species, Excitotoxicity, Neurodegeneration, Programmed cell death, Cytochrome, Parkinson's disease, Neurotrophic factors, Nerve growth factor, Basic fibroblast growth factor, Brain-derived neurotrophic factor, Amyloid plaques, Neurofibrillary tangles, Amyloid b, Tau proteins, Presenilin, Autophagy, Ursodeoxycholic acid, Tauroursodeoxycholic acid, Interleukin, VX-765, IDN-6556, LB-84451, Pralnacasan, ZVAD-fmk, Ac-YVAD-cmk, Z-DEVD-fmk, ZVAD-DCB, Caspase inhibitors, Humanin, Neuroprotection