Dysregulated Plasma Membrane Turnover Underlying Dendritic Pathology in Neurodegenerative Diseases

Abstract

Due to their enormous surface area compared to other cell types, neurons face unique challenges in properly handling supply and retrieval of the plasma membrane (PM)-a process termed PM turnover-in their distal areas. Because of the length and extensiveness of dendritic branches in neurons, the transport of materials needed for PM turnover from soma to distal dendrites will be inefficient and quite burdensome for somatic organelles. To meet local demands, PM turnover in dendrites most likely requires local cellular machinery, such as dendritic endocytic and secretory systems, dysregulation of which may result in dendritic pathology observed in various neurodegenerative diseases (NDs). Supporting this notion, a growing body of literature provides evidence to suggest the pathogenic contribution of dysregulated PM turnover to dendritic pathology in certain NDs. In this article, we present our perspective view that impaired dendritic endocytic and secretory systems may contribute to dendritic pathology by encumbering PM turnover in NDs.

Dendritic spine loss deep in the neocortex and dendrite distortion with diffusion disturbances occur early in experimental pneumococcal meningitis

“…It is not uncommon in other diseases to observe initial degeneration of distant compartments before degeneration of the neural body. Most studies investigating processes of neuronal damage have focused on axonal damage (such as in multiple sclerosis, meningitis, and many other conditions) (Coleman and Perry, 2002;Nau et al, 2004). Axons are particularly vulnerable to transport disturbances due to the proportionally higher need for active transport, their small diameter, and (often) substantial length.…”

“…Local synthesis complements transport due to the need to overcome longer distances, especially in the neocortex, where dendrites can reach significant lengths ( Eberwine et al, 2001 ). Dendrite degeneration in the presence of intracellular aggregates (in Alzheimer’s disease, Huntington’s disease, and others), extracellular toxic factors, and metabolic challenges is known, and disturbances of dendritic transport are suggested to play a role in these processes ( Park et al, 1996 ; Scheff and Price, 2003 ; Lee et al, 2011 ; Kelley et al, 2019 ; Chung et al, 2020 ). The removal of PLY eliminated the dendritic bending effect, confirming the role of cytolysin in it, and the sensitivity of dendrites to the toxin ( Figure 4B ).…”

Mesencephalic Astrocyte-Derived Neurotrophic Factor Regulates Morphology of Pigment-Dispersing Factor-Positive Clock Neurons and Circadian Neuronal Plasticity in Drosophila melanogaster

“…The lack of DmMANF in L2 neurons abolished the daily changes in morphology of their dendritic tree. A constant turnover of the plasma membrane of neurons, which is needed for maintaining the morphology and the remodelling of the dendritic tree, is mediated primarily by endocytic and secretory pathways (Chung et al, 2020). Microarray studies have shown that lack of DmMANF results in downregulation of several genes in the exocytosis pathway (Palgi et al, 2012).…”