Unraveling the molecular mechanisms of aluminium chloride-induced Alzheimer's disease.

The most prevalent neurodegenerative illness is Alzheimer's disease (AD). Aluminium chloride (AlCl3) is a heavy metals that produces several neurodegenerative diseases, commonly AD. AlCl3 easily goes through the blood-brain barrier and reaches to brain. In this study, we reviewed literature, highlighting the various molecular mechanisms targeting AlCl3-induced neurodegenerative disorders like AD in numerous in vivo and in vitro models. AlCl3 can cause conformational changes in the beta-sheet of amyloid beta (Aβ) peptide that lead to the aggregation of Aβ in the brain's neuronal cells. AlCl3 can also decrease the expression of protein phosphatase 2A (PP2A), which is essential for evading tau aggregation and neurofibrillary tangles (NFTs) formation. It can increase acetylcholinesterase (AChE) levels in the brain, which can produce cognitive impairment. AlCl3 also produces calcium (Ca2+) and iron dyshomeostasis in neuronal cells. It activates various inflammatory mediators such as interleukin-6 (IL-6), interleukin-1β (IL-1β), plasminogen activator inhibitor-1 (PAI-1), and tumour necrosis factor-α (TNF-α). In addition, AlCl3 can increase the production of reactive oxygen species (ROS), which induce telomere degradation, may initiate telomere dysfunction that can initiate neuroinflammation, and induce cellular senescence. AlCl3 may increase the expression of glycogen synthase kinase-3 beta (GSK3β), which produces various cognitive impairments, leading to AD. Various therapeutic techniques like chelation, antioxidant, and drug therapy are used to treat AD, but a better-targeted approach and a deeper understanding of the molecular basis of Alzheimer's due to AlCl3 intoxication are crucial. AlCl3-induced neurotoxicity involves mitochondrial disruption, oxidative stress, neuroinflammation, and DNA impairment, necessitating further research for treatment against aluminium (Al)-induced AD. AlCl3 can cause neurodegenerative diseases like AD, but understanding its molecular mechanisms is challenging due to its interaction with biological systems.