Publication Date:
2019
Description:
〈sec〉〈st〉Synopsis〈/st〉〈p〉〈textbox textbox-type="graphic"〉〈p〉〈inline-fig〉〈/inline-fig〉〈/p〉〈/textbox〉〈/p〉
〈p〉Abnormal TDP-43 function culminate in impaired secretion of neurotrophin BDNF, whose restoration is sufficient to rescue major disease phenotypes caused by aberrant TDP-43 activity.〈/p〉
〈p〉 〈l type="unord"〉〈li〉〈p〉Knockdown, aggregation or disease-associated mutation of TDP-43 impair intracellular sorting and activity-dependent secretion of the neurotrophin brain-derived neurotrophic factor (BDNF) through altered splicing of the trafficking receptor Sortilin.〈/p〉〈/li〉
〈li〉〈p〉Human neurons derived from patient iPSCs carrying mutated TDP-43 also show altered Sortilin splicing and reduced levels of activity-dependent BDNF secretion, which can be restored by correcting the mutation.〈/p〉〈/li〉
〈li〉〈p〉Major disease phenotypes caused by aberrant TDP-43 activity may be explained by the abnormal function of a handful of critical proteins, such as BDNF.〈/p〉〈/li〉〈/l〉 〈/p〉〈/sec〉
Print ISSN:
0261-4189
Electronic ISSN:
1460-2075
Topics:
Biology
,
Medicine
