Abstract
In the last years, different kinds of limbic encephalitis associated with autoantibodies against ion channels and synaptic receptors have been described. Many studies have demonstrated that such autoantibodies induce channel or receptor dysfunction. The same mechanism is discussed in immune-mediated cerebellar ataxias (IMCAs), but the pathogenesis has been less investigated. The aim of the present review is to evaluate what kind of cerebellar ion channels, their related proteins, and the synaptic machinery proteins that are preferably impaired by autoantibodies so as to develop cerebellar ataxias (CAs). The cerebellum predictively coordinates motor and cognitive functions through a continuous update of an internal model. These controls are relayed by cerebellum-specific functions such as precise neuronal discharges with potassium channels, synaptic plasticity through calcium signaling pathways coupled with voltage-gated calcium channels (VGCC) and metabotropic glutamate receptors 1 (mGluR1), a synaptic organization with glutamate receptor delta (GluRδ), and output signal formation through chained GABAergic neurons. Consistently, the association of CAs with anti-potassium channel-related proteins, anti-VGCC, anti-mGluR1, and GluRδ, and anti-glutamate decarboxylase 65 antibodies is observed in IMCAs. Despite ample distributions of AMPA and GABA receptors, however, CAs are rare in conditions with autoantibodies against these receptors. Notably, when the autoantibodies impair synaptic transmission, the autoimmune targets are commonly classified into three categories: release machinery proteins, synaptic adhesion molecules, and receptors. This physiopathological categorization impacts on both our understanding of the pathophysiology and clinical prognosis.
Highlights
Autoantibodies of ion channels and receptors can elicit neurological symptoms [1]
The aim of the present review is to evaluate what kind of cerebellar ion channels, their related proteins, and the synaptic machinery proteins that are preferably impaired by autoantibodies so as to develop cerebellar ataxias (CAs)
Recent studies have documented the association of CAs with autoantibodies toward leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (Caspr2), dipeptidyl-peptidase-like protein-6 (DPPX), AMPA, GluRδ, GABA, and glycine-receptors, the data regarding clinical specificities and pathophysiological profiles are scarce due to the rare prevalence of these conditions
Summary
Autoantibodies of ion channels and receptors can elicit neurological symptoms [1]. In the past two decades, there has been accumulating physiological and clinical evidence showing that autoantibodies against potassium channel-associated proteins, glutamate receptors, and GABA receptors impair neural excitability or synaptic transmission, resulting in limbic encephalitis [2,3,4,5]. The aim of the present review is to evaluate what kind of cerebellar ion channels, their related proteins, and the synaptic machinery proteins that are preferably impaired by autoantibodies so as to develop cerebellar ataxias (CAs). The cerebellar targets of autoantibodies are classified physiologically into two categories of ion channels and synaptic transmission-related proteins. The latter could be further classified into: 1. We argue that the categorization of synaptic targets could be related to clinical prognosis
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