Abstract
Huntington's disease (HD) is a neurodegenerative disorder characterized by selective loss of neurons in the striatum and cortex, which leads to progressive motor dysfunction, cognitive decline, and psychiatric disorders. Although the cause of HD is well described—HD is a genetic disorder caused by a trinucleotide (CAG) repeat expansion in the gene encoding for huntingtin (HTT) on chromosome 4p16.3—the ultimate cause of neuronal death is still uncertain. Apart from impairment in systems for handling abnormal proteins, other metabolic pathways and mechanisms might contribute to neurodegeneration and progression of HD. Among these, inflammation seems to play a role in HD pathogenesis. The current review summarizes the available evidence about immune and/or inflammatory changes in HD. HD is associated with increased inflammatory mediators in both the central nervous system and periphery. Accordingly, there have been some attempts to slow HD progression targeting the immune system.
Highlights
Huntington’s disease (HD) is a neurodegenerative disorder characterized by selective loss of neurons in the striatum and cortex, which leads to progressive motor dysfunction, cognitive decline, and psychiatric disorders [1]
HD is a genetic disorder caused by a trinucleotide (CAG) repeat expansion in the gene encoding for huntingtin (HTT) on chromosome 4p16.3
As observed in patients, increased microglial activation was detected in the striatum of presymptomatic R6/2 mice [13]
Summary
Huntington’s disease (HD) is a neurodegenerative disorder characterized by selective loss of neurons in the striatum and cortex, which leads to progressive motor dysfunction, cognitive decline, and psychiatric disorders [1]. HD is a genetic disorder caused by a trinucleotide (CAG) repeat expansion in the gene encoding for huntingtin (HTT) on chromosome 4p16.3. Mutated HTT with 40 or more CAG repeats results in HD with complete penetrance. The CAG repeat expansion in HTT encodes an expanded polyglutamine tract in the huntingtin (HTT) protein resulting in a mutant protein [1]. The neuronal death observed in HD might result from loss of function and/or gain of toxicity of mutant HTT, but a range of evidence suggests that HD arises mainly from gain of toxicity from an abnormal conformation of mutant HTT [5]. Apart from modulating immune cell functions, inflammatory mediators act on neurons, possibly contributing to neuronal death. Neuronal death further activates inflammatory mechanisms, resulting in a vicious cycle of inflammation and neurodegeneration [7]. We briefly presented the studies targeting immune disruption as an attempt to slow disease progression
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