治疗阿尔兹海默症的靶向肿瘤坏死因子α

Title:Targeting Tumor Necrosis Factor Alpha for Alzheimer’s Disease

Volume: 14 Issue: 4

关键词: 阿尔兹海默症，BACE1，伊那西普，炎症，神经性炎症，沙利度胺，TNF-α

摘要: Alzheimer’s disease (AD) affects an estimated 44 million individuals worldwide, yet no therapeutic intervention is available to stop the progression of the dementia. Neuropathological hallmarks of AD are extracellular deposits of amyloid beta (Aβ) peptides assembled in plaques, intraneuronal accumulation of hyperphosphorylated tau protein forming tangles, and chronic inflammation. A pivotal molecule in inflammation is the pro-inflammatory cytokine TNF-α. Several lines of evidence using genetic and pharmacological manipulations indicate that TNF-α signaling exacerbates both Aβ and tau pathologies in vivo. Interestingly, preventive and intervention anti-inflammatory strategies demonstrated a reduction in brain pathology and an amelioration of cognitive function in rodent models of AD. Phase I and IIa clinical trials suggest that TNF-α inhibitors might slow down cognitive decline and improve daily activities in AD patients. In the present review, we summarize the evidence pointing towards a beneficial role of anti-TNF-α therapies to prevent or slow the progression of AD. We also present possible physical and pharmacological interventions to modulate TNF-α signaling in AD subjects along with their limitations.

Cite this article as:

Targeting Tumor Necrosis Factor Alpha for Alzheimer’s Disease, Current Alzheimer Research 2017; 14 (4) . https://dx.doi.org/10.2174/1567205013666160930110551