Fyn Kinase in Alzheimer’s Disease: Unraveling Molecular Mechanisms and Therapeutic Implications

Alzheimer’s disease, characterized by the accumulation of abnormal protein aggregates and neuronal damage in the brain, leads to a gradual decline in cognitive function and memory. As a complex neurodegenerative disorder, it involves disruptions in various biochemical pathways and neurotransmitter systems, contributing to the progressive loss of neurons and synaptic connections. The complexity of Alzheimer’s signaling pathways complicates treatment, presenting a formidable challenge in the quest for effective therapeutic interventions. A member of the Src family of kinases (SFKs), Fyn, is a type of non-receptor tyrosine kinase that has been linked to multiple essential CNS processes, such as myelination and synaptic transmission. Fyn is an appealing target for AD treatments because it is uniquely linked to the two major pathologies in AD by its interaction with tau, in addition to being activated by amyloid-beta (Aβ) through PrPC. Fyn mediates neurotoxicity and synaptic impairments caused by Aβ and is involved in regulating the process of Aβ synthesis. Additionally, the tau protein’s tyrosine phosphorylation is induced by Fyn. Fyn is also a challenging target because of its widespread body expression and strong homology with other kinases of the Src family, which could cause unintentional off-target effects. This review emphasizes signaling pathways mediated by Fyn that govern neuronal development and plasticity while also summarizing the most noteworthy recent research relevant to Fyn kinase’s function in the brain. Additionally, the therapeutic inhibition of Fyn kinase has been discussed, with a focus on the Fyn kinase inhibitors that are in clinical trials, which presents a fascinating opportunity for targeting Fyn kinase in the creation of possible therapeutic approaches for the management of Alzheimer’s disease.