The Emerging Key Role of the mGluR1-PKCγ Signaling Pathway in the Pathogenesis of Spinocerebellar Ataxias: A Neurodevelopmental Viewpoint

Abstract

Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal dominantly inherited progressive disorders with degeneration and dysfunction of the cerebellum. Although different subtypes of SCAs are classified according to the disease-associated causative genes, the clinical syndrome of the ataxia is shared, pointing towards a possible convergent pathogenic pathway among SCAs. In this review, we summarize the role of SCA-associated gene function during cerebellar Purkinje cell development and discuss the relationship between SCA pathogenesis and neurodevelopment. We will summarize recent studies on molecules involved in SCA pathogenesis and will focus on the mGluR1-PKCγ signaling pathway evaluating the possibility that this might be a common pathway which contributes to these diseases.

Focusing on the Emerging Role of Kainate Receptors in the Dorsal Cochlear Nucleus (DCN) and Cerebellum

“…As intricate nerve networks are mediated and connected by synapses, glutamate is an important neurotransmitter that acts through glutamate receptors in the brain, including the DCN and cerebellum [ 9 , 10 , 11 ]. For example, as a classical metabolic glutaminergic receptor, mGluR1 has been well studied in both the DCN and cerebellum [ 12 , 13 , 14 , 15 ]. However, kainate receptors (KARs), as a class of ionotropic glutamate receptors, and their role in the DCN and cerebellum are far from being fully explored, and studies of their distribution in these structures in earlier years were also relatively preliminary.…”

Computational models of neurotransmission at cerebellar synapses unveil the impact on network computation

“…Some subtypes of GoC are endowed with mGluR2 and mGluR5, while mGluR4 is restricted to parallel fibers ( Knöpfel and Grandes, 2002 ). This receptor mediates slow electrical responses through TRPC channels that, in the case of PCs, are critical for the development and maintenance of the dendritic structure ( Wu and Kapfhammer, 2022 ).…”