Neuromuscular tissue-derived factors and inflammatory-cell-targeted nanoparticles for advancing brain health
Huang, Kai-Yu
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https://hdl.handle.net/2142/125783
Description
Title
Neuromuscular tissue-derived factors and inflammatory-cell-targeted nanoparticles for advancing brain health
Author(s)
Huang, Kai-Yu
Issue Date
2024-07-07
Director of Research (if dissertation) or Advisor (if thesis)
Kong, Hyunjoon
Doctoral Committee Chair(s)
Kong, Hyunjoon
Committee Member(s)
Leckband, Deborah E.
Gazzola, Mattia
Su, Xiao
Department of Study
Chemical & Biomolecular Engr
Discipline
Chemical Engineering
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Neuromuscular Junction
Tissue Engineering
Myokine
Exosome
Nanoparticle Transport
Blood-brain Barrier
Language
eng
Abstract
Neurological disorders often lead to denervation and muscle atrophy, resulting multi-organ dysfunction and homeostasis compromise. These adverse outcomes may be linked to altered biologic secretion from muscles in response to neuromuscular junction (NMJ) degradation, yet the mechanisms remain poorly understood. Concurrently, engineered nanoparticles have shown promise as drug delivery systems for enhancing the bioavailability and retention of therapeutic agents in brain. However, the influence of aging and neuropathology on nanoparticle transport across the blood-brain barrier (BBB) has not been fully elucidated. This dissertation aims to investigate the impact of neuronal innervation on skeletal muscle secretion and to design nanoparticles that probe BBB permeability alterations due to brain disorders and aging. Chapter 1 introduces skeletal muscle-secreted factors, NMJ models, and nanoparticle delivery strategies for BBB traversal. Chapter 2 details an in vitro neuromuscular model illustrating the regulation of muscle secretion by neuronal innervation and the effect of muscle-derived factors on neuronal development. In Chapter 3, the enhancement of neurotrophic exosome secretion from neuromuscular tissues via IGF-1 is explored, assessing its impact on neural network formation and function. Chapter 4 focuses on the design of nanoparticles targeting inflamed brain cells and investigates how Alzheimer’s disease and aging modulate intracerebral nanoparticle transport. Finally, Chapter 5 consolidates the findings from Chapters 2 to 4 and outlines prospective research trajectories.
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