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.