Biology subjects

Kipingi, L. K.

Publications and source records attributed to Kipingi, L. K..

2 recordsLinked to original sources

bioRxiv2026

Giant spider neurons uncover a myelin-derived waste-internalizing canal system that fails in neurodegeneration

The underlying causes for Alzheimer disease are presumed to lie in failed waste removal from the brain. However, the mechanisms by which waste is cleared from neurons, and how this system fails in neurodegeneration are poorly understood. A novel glial-canal-hypothesis postulates that myelin-forming macroglia give rise to waste internalizing canals that project into neuronal somata and remove cellular debris in an aquaporin4-dependent manner. We postulate that abnormal swelling of the aquaporin4-expressing glial cells leads to spongiform abnormalities, gradual depletion, and death of associated neurons. Due to the novelty of this postulation little is known about the cellular architecture of this canal system that was first discovered in giant neurons of the wandering spider Cupiennius salei. Here we have utilized histological, ultrastructural and immunohistochemical methods to describe the structural foundation of this glial canal system in giant spider neurons in which waste-internalizing canals and associated structures are clearly visible. Sequencing the spider genome, we show compelling homologies of key proteins that are implicated in neurodegeneration between phylogenetically distant species. Based on this work, we provide a testable functional hypothesis regarding waste removal from neuronal somata and how this system fails in neurodegeneration. We highlight structural similarities of this system in rodent and human brain. Supported by the findings presented here we postulate that (i) neurodegeneration in C. salei may be caused by hypertrophic swelling of myelin-forming waste-internalizing macroglia, and (ii) that a similar canal system, although structurally modified, is likely highly conserved in the mammalian brain.

neuroscience↗

bioRxiv2025

Uncovering the invisible giant: Amyloid β plaques and their proposed association with waste removal in Alzheimer-affected human hippocampus

According to the prevalent Amyloid Hypothesis, the underlying cause for neurodegeneration in Alzheimer Disease (AD) is attributed to the accumulation of misfolded Amyloid {beta} and tau protein in the form of extracellular sticky plaques and neurofibrillary tangles respectively. These protein accumulations are thought to be caused by impaired waste removal. In an alternative hypothesis, we have proposed the existence of an extensive glial canal system that is likely formed by myelinated aquaporin-4 (AQP4)-expressing tanycytes and removes cellular waste from the hippocampal formation. Here, we demonstrate that tanycyte-derived waste-internalizing receptacles are immunoreactive for A{beta} and emanate from specialized nucleus-like organelles in the following referred to as tanysomes. Utilizing RNA-scope in situ hybridization, we demonstrate that these receptacle-forming tanysomes express RNA for AQP4 and the A{beta}-related genes, amyloid precursor protein, and presenilin 1. These findings suggest that A{beta} is likely synthesized where receptacle formation is observed and that A{beta} may play an important structural role in receptacle formation. In AD-affected hippocampus excessive amounts of A{beta}-immunoreactive waste receptacles emerge from tanysomes and have the appearance of plaques in A{beta}-immunolabeled hippocampus. Moreover, we demonstrate that the same receptacle-forming organelles exhibit strong immunolabeling for hyperphosphorylated tau protein in AD-affected tissue. We postulate that both proteins may play important structural roles in waste uptake and that hypertrophic swelling of impaired tanycytes in AD-affected brain may be due to obstructions of this extensive interconnected glial canal system.

neuroscience↗