NAD+-dependent mechanism of pathological axon degeneration

Ying Cao; Yi Wang; Jing Yang

doi:10.1016/j.cellin.2022.100019

NAD⁺-dependent mechanism of pathological axon degeneration

Cell Insight. 2022 Mar 4;1(2):100019. doi: 10.1016/j.cellin.2022.100019. eCollection 2022 Apr.

Authors

Ying Cao^{1

2}, Yi Wang^{1

2}, Jing Yang^{1

3

4

5

6}

Affiliations

¹ Center for Life Sciences, Peking University, Beijing, 100871, China.
² Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
³ State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, 100871, China.
⁴ IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
⁵ Chinese Institute for Brain Research, Beijing, 102206, China.
⁶ Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, 518055, China.

Abstract

Pathological axon degeneration is broadly observed in neurodegenerative diseases. This unique process of axonal pathology could directly interfere with the normal functions of neurocircuitries and contribute 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, the research field has witnessed 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 novel NAD⁺-dependent mechanism involving the WLD^s, NMNAT2, and SARM1 proteins has emerged. This review summarizes the landmark discoveries elucidating the molecular pathway of pathological axon degeneration and highlights the evolving concept that neurodegeneration would be intrinsically linked to NAD⁺ and energy metabolism.

Keywords: Energy deficit; NAD+ metabolism; Pathological axon degeneration; SARM1; Wlds mutation.

Publication types

Review