Non-Steroidal Anti-Inflammatory Drugs as Anti-Amyloidogenic Compounds

Author(s): Mie Hirohata, Kenjiro Ono, Masahito Yamada.

Journal Name: Current Pharmaceutical Design

Volume 14 , Issue 30 , 2008

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Abstract:

Amyloidosis is a clinical disorder caused by deposition of proteins that abnormally self-assemble into insoluble fibrils and impair organ function. More than 20 unrelated precursor proteins lose their native structure and misfold, leading to the formation of amyloid fibrils. The latter share cross-β core structure in vivo and in vitro and gain abnormal functions. Local amyloid deposition occurs in the central nervous system in Alzheimers disease (AD) and cerebral amyloid angiopathy. AD is the most common form of neurodegenerative disorder, with dementia in the elderly as well as dementia with Lewy bodies (DLB). Extracellular deposition of amyloid β-peptide (Aβ) has been implicated as a critical step in the pathogenesis of AD. Involvement of neuroinflammation and microglial activation has been emphasized in the AD brain. Recent epidemiological studies have shown that long-term therapeutic use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of developing AD and delayed the onset of AD. We review epidemiological studies of anti-AD effects of NSAIDs, experimental studies of anti-amyloidogenic as well as anti-inflammatory effects of NSAIDs, and recent clinical trials for AD with NSAIDs. We refer to the anti-fibrillogenic and fibril-destabilizing activities of NSAIDs for other proteins that can aggregate and form amyloid-like fibrils, including α-synuclein in DLB. The anti-amyloidogenic properties of some NSAIDs provide new insights for future therapeutic and preventative opportunities for AD and other amyloidoses, and protein-misfolding disorders.

Keywords: Alzheimer's disease, amyloid β-peptide (Aβ), amyloidosis, α-synuclein fibrils, central nervous system, neuroinflammation, non-steroidal anti-inflammatory drugs (NSAIDs), protein-misfolding disorders

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Article Details

VOLUME: 14
ISSUE: 30
Year: 2008
Page: [3280 - 3294]
Pages: 15
DOI: 10.2174/138161208786404173
Price: $58

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