title: Molecular basis of etiological implications in Alzheimer's disease: focus on neuroinflammation.
abstract: Significant bodies of evidences have shown different mechanisms known to be the etiological cause of Alzheimer's disease (AD) involving amyloid-beta protein accumulation, chronic inflammatory reactions, oxidative stress, proteasome inhibition, and high-cholesterol level, but the presize etiology of AD still remains enigmatic. Recent studies indicate that these mechanisms seem to be interlinked, and neuroinflammation emerges as a major regulatory and commen factor in all these mechanisms. In amyloid-beta protein, induced neurodegenerative hypothesis of AD inflammatory cytokines IFN-γ, TNF-α, interleukin (IL)-1α plays an important role in the progression of the disease. In cholesterol induced hypothesis liver X receptor mediated IL-4 also plays a major role in the progression of neuroinflammation. Notably, Omi and HtrA2 proteases play very important functions in neuronal dysfunction, which may lead to neurodegeneration. Further at genetic level, alterations in the genes occur especially in APP, PSEN1, PSEN2, APO E(ε4), ADAM12, and SH3MD1 which mediate neurodegeneration. Additionaly, The role of SP-1, NF-κB, and BCAE-1 is critical in the regulation of neuroinflammation-associated disease pathogenesis. All together, in this review, we discus the importance of neuroinflammatory mediators and their mechanistic role in the process of AD neurodegeneration.
authors: Division of Gastroenterology and Liver Diseases, School of Medicine, Case Western Reserve University, 2109 Adelbert Rd., BRB 501, Cleveland, OH, 44106, USA, riturajniranjan@rediffmail.com.
authors: Rituraj
authors: R
authors: Niranjan
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology; D009420:Nervous System / Q000473:pathology*
chemical_list: D016229:Amyloid beta-Peptides; D002784:Cholesterol