A Comprehensive Review of Autophagy and Its Various Roles in Infectious, Non-Infectious, and Lifestyle Diseases: Current Knowledge and Prospects for Disease Prevention, Novel Drug Design, and Therapy

Abstract

Autophagy (self-eating) is a conserved cellular degradation process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, and infection-mediated stresses. Autophagy dysfunction can have various pathological consequences, including tumor progression, pathogen hyper-virulence, and neurodegeneration. This review describes the mechanisms of autophagy and its associations with other cell death mechanisms, including apoptosis, necrosis, necroptosis, and autosis. Autophagy has both positive and negative roles in infection, cancer, neural development, metabolism, cardiovascular health, immunity, and iron homeostasis. Genetic defects in autophagy can have pathological consequences, such as static childhood encephalopathy with neurodegeneration in adulthood, Crohn’s disease, hereditary spastic paraparesis, Danon disease, X-linked myopathy with excessive autophagy, and sporadic inclusion body myositis. Further studies on the process of autophagy in different microbial infections could help to design and develop novel therapeutic strategies against important pathogenic microbes. This review on the progress and prospects of autophagy research describes various activators and suppressors, which could be used to design novel intervention strategies against numerous diseases and develop therapeutic drugs to protect human and animal health.

Review: Danon disease: Review of natural history and recent advances

“…DD was originally postulated to be caused by a glycogen storage defect of glycogen accumulation in lysosomes. However, recent studies have shown that the underlying mechanism is a block in autophagy leading to impaired fusion of autophagosome–lysosome and/or inefficient lysosome biogenesis and maturation .…”

“…Progress and prospects in the therapeutic field of autophagy‐associated disease have highlighted new categories of potential drugs, including autophagy activators (mTOR‐mammalian target of rapamycin, treholase, fluoxetine) and inhibitors (bafilomycin, chloroquine, cycloheximide), which could be used in the near future to design novel intervention strategies .…”

Succinic Semialdehyde Dehydrogenase Deficiency: An Update

“…In line with this, SSADH deficient mice exhibit increased numbers of mitochondria that show morphological defects, which would be consistent with impaired mitophagy [60]. Defects in autophagy are also associated with diverse neurodegenerative disorders, including the neuronal ceroid lipofuscinoses, Alzheimer's disease and Parkinson's disease, which also show mitochondrial dysfunction and increased oxidative stress [61,63].…”

Hyperthermia Increases Neurotoxicity Associated with Novel Methcathinones

“…In support of this assumption, it has been shown that 3-fluoromethcathinone (3-FMC), another synthetic methcathinone, activates autophagy in the neuronal cell line HT22 [45]. Autophagy is an evolutionarily conserved process, which plays a pivotal role in maintaining the viability of eukaryotic organisms by regulating the intracellular balance between anabolism and catabolism [46]. Autophagy is activated as a protective mechanism when cells are not able to respond to nutrient stress, the accumulation of misfolded proteins, and/or organelle damage [47].…”