{Reference Type}: Journal Article
{Title}: Pathologic TDP-43 downregulates myelin gene expression in the monkey brain.
{Author}: Zhu L;Bai D;Wang X;Ou K;Li B;Jia Q;Tan Z;Liang J;He D;Yan S;Wang L;Li S;Li XJ;Yin P;
{Journal}: Brain Pathol
{Volume}: 0
{Issue}: 0
{Year}: 2024 May 23
{Factor}: 7.611
{DOI}: 10.1111/bpa.13277
{Abstract}: Growing evidence indicates that non-neuronal oligodendrocyte plays an important role in Amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In patient's brain, the impaired myelin structure is a pathological feature with the observation of TDP-43 in cytoplasm of oligodendrocyte. However, the mechanism underlying the gain of function by TDP-43 in oligodendrocytes, which are vital for the axonal integrity, remains unclear. Recently, we found that the primate-specific cleavage of truncated TDP-43 fragments occurred in cytoplasm of monkey neural cells. This finding opened up the avenue to investigate the myelin integrity affected by pathogenic TDP-43 in oligodendrocytes. In current study, we demonstrated that the truncated TDP-35 in oligodendrocytes specifically, could lead to the dysfunctional demyelination in corpus callosum of monkey. As a consequence of the interaction of myelin regulatory factor with the accumulated TDP-35 in cytoplasm, the downstream myelin-associated genes expression was downregulated at the transcriptional level. Our study aims to investigate the potential effect on myelin structure injury, affected by the truncated TDP-43 in oligodendrocyte, which provided the additional clues on the gain of function during the progressive pathogenesis and symptoms in TDP-43 related diseases.