Posts by Eli Vidhammer

Welcome to the Neuro-SysMed monthly seminars! Topic this time is Key roles of NAD metabolism in neurodegeneration, and speaker is Mathias Ziegler. Join us in the auditorium in Armauer Hansens Hus at 11:30–13:00 (lunch 11:30–12:00).

SpeakerMathias Ziegler

Title: Key roles of NAD metabolism in neurodegeneration

Place: The auditorium in Armauer Hansens Hus (campus Haukeland University Hospital)

Time: Wednesday September 13 at 11:30 – 13:00 (lunch from 11:30 – 12:00).

Registration link: please use this link

Lecture language: English

Who: All are welcome

Abstract: Rapid degeneration of an axon distal to an injury has been described in 1850 by A. Waller – and is therefore referred to as Wallerian degeneration. Only recently the mechanisms of this process have been identified. Instrumental to this achievement was the discovery of a mouse strain (WldS – Wallerian degeneration slow) that exhibits a substantially slower axon degeneration upon injury. Genetic analyses revealed that the delay in degeneration was caused by the triplication of a gene encoding an enzyme (NMNAT1) critical for NAD biosynthesis, thereby providing the first link between neurodegeneration and NAD metabolism.

Recently, another key player in Wallerian degeneration was discovered to be SARM1. It turned out that SARM1 is a highly regulated NAD-cleaving enzyme. When activated, it can rapidly deplete intracellular NAD, thereby leading to cell (or axonal) death. Apparently, this is counteracted in WldS mice by enhancing NAD biosynthesis. Intriguingly, GWAS have indicated a linkage between ALS and the SARM1 locus.

Our recent work has established that SARM1 activity can be induced chemically in various cell lines indicating that mechanical injury is not necessarily required to trigger this pathway in axons. Moreover, we revealed that the SARM1-mediated cell death pathway is not unique for neurons, but rather wide-spread. However, it requires the presence of NMNAT2, an NAD biosynthetic enzyme highly expressed in the brain. The tools and cellular model systems we have generated will be valuable in further dissecting the mechanisms of Wallerian degeneration. Importantly, they will enable testing of therapeutic approaches to treat neurodegenerative diseases that may involve NAD- and SARM1-mediated cell death pathways.

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