Neuromuscular tissue-derived factors and inflammatory-cell-targeted nanoparticles for advancing brain health

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemical Engineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2024

Author dc:creator

• Huang, Kai-Yu

Contributors dc:contributor

• Kong, Hyunjoon
• Leckband, Deborah E.
• Gazzola, Mattia
• Su, Xiao

• Neuromuscular Junction
• Tissue Engineering
• Myokine
• Exosome
• Nanoparticle Transport
• Blood-brain Barrier

Statement dc:rights

• Copyright 2024 Kai-Yu Huang

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/125783

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F125783