Pathological axon degeneration is broadly observed in neurodegenerative diseases. This unique process of axonal pathology directly interferes with normal neurophysiological processes and thus contributes to the onset of clinical symptoms in patients. It has been increasingly recognized that functional preservation of axonal structures is an indispensable part of therapeutic strategies for treating neurological disorders. In the past decades, our colleagues and we have achieved significant breakthroughs in understanding the stereotyped self-destruction of axons upon neurodegenerative insults, which is distinct from all the known types of programmed cell death. In particular, the NAD+-dependent mechanism involving the WLDs, NMNAT2, and SARM1 proteins has emerged, establishing the principle that neurodegeneration is intrinsically linked to NAD+-related metabolism.

SELECTED PAPERS

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