Crosstalk between NLRP3 inflammasome and calpain in Alzheimer's disease.

Amyloid plaques are considered to be the pathological hallmark of Alzheimer's disease (AD). Neuroinflammation further aggravates the pathogenesis of Alzheimer's disease. Calpains and NOD-like receptor protein-3 (NLRP3) inflammasomes are involved in the neuroinflammatory pathway and affect the progression of Alzheimer's disease. Hyperactivation of calpains is responsible for the activation of NLRP3 inflammasome, thereby affecting each other's molecular mechanism and causing astrogliosis, microgliosis, and neuronal dysfunction. Further, calpain hyperactivation is also associated with calcium homeostasis that acts as one of the triggers in the activation of NLRP3 inflammasome. Calpain activity is required for the maturation of interleukin-1ß, a key mediator of neuroinflammatory responses. The membrane potential/calcium/calpain/caspase-1 axis acts as an unconventional regulator of inflammasomes. The complex crosstalk between NLRP3 inflammasome and calpain leads to a series of events. Targeting the molecular mechanism associated with calpain-NLRP3 inflammasome activation and regulation can be a therapeutic and prophylactic perspective towards Alzheimer's disease. This review discusses calpains and NLRP3 inflammasome crosstalk in the pathogenesis of AD.

Behavioral and Neurological Effects of Edaravone and Noscapine in Albino Wistar Rats.

OBJECTIVE: The purpose of the study was to explore Edaravone and Noscapine in anAlCl3-induced Alzheimer's disease (AD) model. METHODS: Morris Water Maze (MWM), Novel Object Recognition (NOR), andY-maze tests with TNF-α, IL-1, IL-6, amyloid-ß, CAT, SOD and MDAlevels were performed, followed by brain histology. RESULTS: On the probe trial, the MWM demonstrated a decrease in escape latencyfollowed by an increase in the target quadrant. The NOR showeddiscrimination and recognition index scores and Y-maze, revealed arise in spontaneous alterations. TNF-α, IL-1, IL-6, amyloid-ß, CATand MDA levels increased, while SOD levels dropped. The results werefound to be significant for combination full and half doses (***p <0.001, **p < 0.01). The treated group's histology ofbrain revealed mild neurodegeneration with hippocampal pyknoticnuclei. CONCLUSIONS: Thus, Edaravone and Noscapine can be used for thetreatment of AD. .

Abbreviations: AlCl3: Aluminium chloride; AD: Alzheimer's disease; Aß: Amyloid plaques; APP: amyloid precursor protein; BACE 1: Serum beta-secretase 1; GSK3ß: Glycogen synthase kinase 3 ß; CDK 5: cyclin-dependent kinase-5; NFTs: neurofibrillary tangles; ROS: reactive oxygen species; JNK: c Jun N-terminal kinases; MWM: Morris Water Maze; NOR: Novel Object Recognition (NOR); TNF-α: Tumor necrosis factor -α; CAT: Catalase; SOD: Superoxide Dismutase; MDA: Malondialdehyde.