Inflammatory signaling pathways in the treatment of Alzheimer's disease with inhibitors, natural products and metabolites (Review)

Abstract

The intricate nature of Alzheimer's disease (AD) pathogenesis poses a persistent obstacle to drug development. In recent times, neuroinflammation has emerged as a crucial pathogenic mechanism of AD, and the targeting of inflammation has become a viable approach for the prevention and management of AD. The present study conducted a comprehensive review of the literature between October 2012 and October 2022, identifying a total of 96 references, encompassing 91 distinct pharmaceuticals that have been investigated for their potential impact on AD by inhibiting neuroinflammation. Research has shown that pharmaceuticals have the potential to ameliorate AD by reducing neuroinflammation mainly through regulating inflammatory signaling pathways such as NF-κB, MAPK, NLRP3, PPARs, STAT3, CREB, PI3K/Akt, Nrf2 and their respective signaling pathways. Among them, tanshinone IIA has been extensively studied for its anti-inflammatory effects, which have shown significant pharmacological properties and can be applied clinically. Thus, it may hold promise as an effective drug for the treatment of AD. The present review elucidated the inflammatory signaling pathways of pharmaceuticals that have been investigated for their therapeutic efficacy in AD and elucidates their underlying mechanisms. This underscores the auspicious potential of pharmaceuticals in ameliorating AD by impeding neuroinflammation.

Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

“…Based on the evidence described above, mTOR and AKT pathways, as well as JAK-STAT, and PPARγ, and Notch pathways, constitute other crucial pathways in neuroinflammation [9,[110][111][112][113][114][115]. They represent highly conserved signaling hubs that coordinate neuronal activity and brain development and participate in neuroinflammation.…”

“…They represent highly conserved signaling hubs that coordinate neuronal activity and brain development and participate in neuroinflammation. Accordingly, hyperactivation of JAK/STAT and mTOR and inhibition of PPARγ and AKT signaling have been associated with various neurological complications, including neuroinflammation, apoptosis, and oxidative stress [112][113][114][115]. Remarkably, target modulators have also been described to act during acute and chronic neurological deficits.…”