Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2017 Dec 4;216(12):3903–3916. doi: 10.1083/jcb.201702150

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© 2017 Pan and Chan

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

PMC Copyright notice

Figure 2. — Proposed molecular mechanisms of secondary axon degeneration. Multiple pathological mechanisms converge synergistically on axon degeneration. In a demyelinated axon, disassembly of nodal architecture and its underlying cytoskeleton may lead to voltage-gated sodium channel declustering, increasing sodium ion influx and the metabolic demand of action potential conduction. Impaired axon transport, increased metabolic load, and excitotoxic stress may lead to failure of the Na⁺/K⁺ ATPase, reversal of the NCX, and entry of calcium into the axon. Increased axoplasmic calcium leads to activation of the calcium-dependent protease calpain, which cleaves many putative substrates crucial to axon function, including those associated with the axon cytoskeleton or transport machinery. Overloading of mitochondrial calcium buffering capacity and impairment of mitochondrial transport via disruption of motor proteins and microtubules inhibits ATP production and exacerbates metabolic impairment. Excitotoxic stress further contributes to increased sodium and calcium influx, transmitted through various ion channels. NMDAR, N-Methyl-d-aspartate receptor. AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; Cav, voltage-gated calcium channel; MAP, microtubule-associated protein; Mit, mitochondria; Nav, voltage-gated sodium channel.