Toward Nano-Drug Precision for Neurodegenerative Diseases or Glioma

Abstract

Background: Developing therapeutic or functional supportive therapeutic strategies for neurodegenerative (ND) diseases (NDDs) or tumor as glioma or glioblastoma (GBM) requires an understanding of the molecular and cellular mechanisms underlying crucial physiological components in neuronal life and disease, namely, the mitochondria, epigenetics, and autophagy. The mitochondrion is a highly dynamic organelle that modulates the most pivotal processes of apoptosis, autophagy, and oxidative stress. Impaired mitochondrial biogenesis with/out abnormal mitochondrial dynamics might contribute to mitochondrial dysfunction witnessed in Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS) as well as Parkinson’s disease (PD) or Alzheimer’s disease (AD) and cancer. Accordingly, mitochondria are crucial to the onset and progression of affected memory, movement, and communications, unfortunately. Chapter Aim: The current chapter will highlight, via extensive literature search and in silico analysis, as well as tracing clinical trials done, how mitochondrial dysfunction, epigenetics, and/or autophagy are implicated in NDDs or glioma pathogenesis as neurological disorders drivers or being glioma-cancer hallmarks, which could be a step toward providing nanotherapies targeting these pathways. Discussion: NDDs are associated with special neuronal proteins synthesized by the endoplasmic reticulum, disposed by cellular lysosomes, accumulated, misfolded, and able to aggregate, being prion-like, and moreover, spreading within the nervous system. As a result of dysfunctional cellular-degrading processes, namely, autophagy, these misfolded proteins accumulate, where autophagy is related to apoptosis and the mitochondrial function by various means. Thus, “neuronal autophagic activity” being influenced by epigenetics and/or by the mitochondrial function/health, affecting the onset and progression of NDDs, is now unraveled, with a spotlight on glioma in relation to these axes, for development and precision of nano-anti-epigenetic drugs or nano-autophagy-modulating drugs and nano-mitochondria-directed drugs.