A Spleen Tyrosine Kinase’s Sky in Neuronal Degeneration

Excerpt

With the growing elderly population, neurodegenerative disorders like Alzheimer’s disease (AD) are emerging as a significant public health concern. It is widely acknowledged in the scientific community that the accumulation of neurotoxic aggregates, such as amyloid beta (Aβ), within the central nervous system is a major factor in the development of these disorders. Furthermore, human genome-wide association studies have identified mutations in microglial receptors that may be linked to a number of neurodegenerative diseases [1]. The inability of microglia to effectively clear toxic Aβ and their pro-inflammatory characteristics are believed to play a significant role in the pathogenesis of late-onset AD. Emerging evidence from studies conducted on both AD patients and neurodegenerative mouse models has revealed the significance of triggering receptors expressed on myeloid cells 2 (TREM2), CD33, and CD22 in the progression of AD [2, 3]. These genes have been identified as crucial factors and are enriched in microglia, making them potential risk genes for AD. Genetic manipulation of these receptors has been shown to modulate neuroendocrine function in animal models of disease [4]. The specific major downstream signaling molecules and effector mechanisms of the aforementioned phenomenon have yet to be determined. …