To Study the Effect of Nilotinib, a Tyrosine Kinase Inhibitor, on Learning and Memory and Its Comparison with Nitric Oxide Synthase Inhibitor in an Animal Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a gradual neurodegenerative disorder presenting with cognitive and non-cognitive impairment. Currently approved therapies alleviate symptoms but do not modify disease progression and may be associated with adverse effects. OBJECTIVE: This study aimed to compare the effect of nilotinib (a tyrosine kinase inhibitor) and N ω-nitro-l-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor) as agents that improve learning and memory processes in a scopolamine-induced rat model of AD with memantine. METHODS: Thirty adult male Wistar rats were randomly assigned to five groups (n = 6 in each group). Scopolamine hydrobromide 3 mg/kg i.p. once daily for 7 days was used to induce AD-like cognitive deficits. Behavioural testing (elevated plus maze [EPM] and Morris water maze [MWM]) was performed on days 8 and 9. From day 10, rats were treated with nilotinib (10 mg/kg p.o.), L-NAME (10 mg/kg i.p.), memantine (10 mg/kg p.o.) or saline for 21 days. Behavioural testing was repeated on days 29 and 30. Then, animals were sacrificed, and brain homogenates were prepared for estimation of acetylcholinesterase (AChE), amyloid-beta 1-42 (Aβ1-42) and PARK-7 levels. RESULTS: Scopolamine increased transfer latency in the EPM and escape latency in the MWM and increased AChE and Aβ1-42 levels, but it decreased PARK-7. Both nilotinib and L-NAME significantly reduced transfer latency and escape latency compared to scopolamine (all p < .001). Both treatments reduced AChE and Aβ1-42 levels and increased PARK-7. Nilotinib produced significantly greater improvements than L-NAME (p < .01) with effects comparable to memantine. CONCLUSION: Nilotinib and L-NAME improved cognitive function and modulated cholinergic, amyloid and autophagy-related markers in a rat model of AD. Nilotinib demonstrated superior efficacy to L-NAME and may represent a potential therapeutic strategy for AD. Further studies are warranted to evaluate long-term effects and clinical applicability.