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Pathophysiology of AITD is extremely complicated and still not fully understood, with genetic, environmental and epigenetic factors involved in its development

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Inactivation of Pde8b enhances memory, motor performance, and protects against age-induced motor coordination decay Genes Brain Behav 11 7: 837-47

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However, late dysfunction of the UMN, potentially due to impaired neurotransmission, may in turn affect the excitability in the LMN spared by SMA progression, accelerating motor circuit disruption and worsening symptoms such as muscle weakness

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