Anatomical distribution of Fyn kinase in the human brain in Parkinson's disease

Abstract

Introduction: Fyn kinase is an Src family kinase (SFK) widely expressed in many tissues, including the CNS. Recently, Fyn kinase activation has been associated with pathological mechanisms underlying neurodegenerative diseases and, as such, the role of Fyn dysfunction is under investigation. In particular, Fyn is implicated as a major upstream regulator of neuroinflammation in Parkinson's Disease (PD). Chronic neuroinflammation has been observed not just in the substantia nigra (SN), but also in several key regions of the brain, with disruption associated with symptoms presentation in PD. This study aimed to characterise the anatomical distribution of Fyn in key brain regions affected in PD, namely the prefrontal cortex, hippocampus, striatum and SN.

Methods: Fresh and fixed post-mortem PD brain samples (n = 10) were collected and compared with neurologically healthy age-matched controls (n = 7) to assess markers of Fyn activity and neuroinflammation.

Results: Increased Fyn phosphorylation was observed in SN and striatum of post-mortem samples from PD patients compared with controls. No such increase was observed in the prefrontal cortex or hippocampus. In contrast with previous findings, no increase in microglial activation or astrocyte reactivity was observed in PD brains across regions.

Conclusion: Taken together, these results indicate that Fyn dysfunction may be involved in the pathological processes observed in PD; however, this appears to be independent of inflammatory mechanisms. Further investigations are required to elucidate if increased Fyn activity is a potential cause or consequence of pathological processing in PD.

Keywords: Basal ganglia; Fyn kinase; Neuroinflammation; Non-SRC family; Parkinsonian; Post-mortem.