Journal
NEUROSCIENCE BULLETIN
Volume 30, Issue 2, Pages 253-270Publisher
SPRINGER
DOI: 10.1007/s12264-013-1425-9
Keywords
Alzheimer's disease; environmental factors; corticotrophin-releasing factor; cerebrovascular; metal toxicity; glia; astrocyte; microglia; A beta; kinase; phosphatase; tau; hyperphosphorylation; epigenetic modification; DNA methylation; histone acetylation
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Funding
- National Basic Research Development Program (973 Program) of China [2011CBA00400]
- National Natural Science Foundation of China [91332201]
- Natural Science Foundation of Shanghai Municipality, China [13JC1401500]
- Fund for Medical Emerging Cutting-edge Technology of Shanghai Municipality, China [SHDC12012114]
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Late-onset Alzheimer's disease (LOAD) is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and A beta toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.
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