English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The organization of the axonal cytoskeleton is a key determinant of thenormal function of an axon, which is a long thin projection away from a neuron.Under normal conditions two axonal cytoskeletal polymers microtubules andneurofilaments align longitudinally in axons and are interspersed in axonalcross-sections. However, in many neurotoxic and neurodegenerative disorders,microtubules and neurofilaments segregate apart from each other, withmicrotubules and membranous organelles clustered centrally and neurofilamentsdisplaced to the periphery. This striking segregation precedes abnormal andexcessive neurofilament accumulation in these diseases, which in turn leads tofocal axonal swellings. While neurofilament accumulation suggests theimpairment of neurofilament transport along axons, the underlying mechanism oftheir segregation from microtubules remains poorly understood for over 30years. To address this question, we developed a stochastic multiscale model forthe cross-sectional distribution of microtubules and neurofilaments in axons.The model describes microtubules, neurofilaments and organelles as interactingparticles in a 2D cross-section, and incorporates the stochastic interactionsthese particles through molecular motors. Simulations of the model demonstratethat organelles can pull nearby microtubules together, and in the absence ofneurofilament transport, this mechanism gradually segregates microtubules fromneurofilaments on a time scale of hours, similar to that observed in toxicneuropathies. This suggests that the microtubule-neurofilament segregation issimply a consequence of the selective impairment of neurofilament transport.The model generates the experimentally testable prediction that the rate andextent of segregation will be dependent on the sizes of the moving organellesas well as the density of their traffic.

A Stochastic Multiscale Model that Explains the Segregation of Axonal Microtubules and Neurofilaments in Neurological Diseases