Recent progress in the role of autophagy in neurological diseases

Abstract

Autophagy (here refers to macroautophagy) is a catabolic pathway by which large protein aggregates and damaged organelles are first sequestered into a double-membraned structure called autophago-some and then delivered to lysosome for destruction. Recently, tremen-dous progress has been made to elucidate the molecular mechanism and functions of this essential cellular metabolic process. In addition to being either a rubbish clearing system or a cellular surviving program in response to different stresses, autophagy plays important roles in a large number of pathophysiological conditions, such as cancer, diabetes, and especially neurodegenerative disorders. Here we review recent progress in the role of autophagy in neurological diseases and discuss how dysregulation of autophagy initiation, autophagosome formation, maturation, and/or au-tophagosome-lysosomal fusion step contributes to the pathogenesis of these disorders in the nervous system.

Dysregulation of Autophagy, Mitophagy, and Apoptosis Genes in the CA3 Region of the Hippocampus in the Ischemic Model of Alzheimer’s Disease in the Rat

“…But data from CA3 area suggest a possible effective protective and slowing role of the BECN1 gene against the progressive death of neurons 30 days after ischemic brain injury. Beclin 1, a key factor in the formation of autophagosomes, has been shown to be suppressed both at the level of mRNA and protein in the brains cortex of patients with early AD [17]. We partially confirmed the above decrease in BECN1 gene expression in brains from AD patients in the ischemic CA3 region of the hippocampus within 2-7 days after ischemia, but we observed increased gene expression on day 30 after ischemia and this difference may result from inability to study gene expression at specific time points and brain structures during the development of AD in patients.…”

“…We partially confirmed the above decrease in BECN1 gene expression in brains from AD patients in the ischemic CA3 region of the hippocampus within 2-7 days after ischemia, but we observed increased gene expression on day 30 after ischemia and this difference may result from inability to study gene expression at specific time points and brain structures during the development of AD in patients. Autophagy dysfunction is referred as a secondary pathologic mechanism for the development of neurodegenerative diseases, such as AD and probably ischemic neurodegeneration [14,17,18]. Finally, some studies indicate that BECN1 gene plays an important role in the processing of the amyloid-␤ protein precursor (A␤PP), as well as in the autophagy removal of proteins susceptible to aggregation from the brains of patients with AD and probably also in ischemic neurodegeneration [17,18].…”

“…Autophagy dysfunction is referred as a secondary pathologic mechanism for the development of neurodegenerative diseases, such as AD and probably ischemic neurodegeneration [14,17,18]. Finally, some studies indicate that BECN1 gene plays an important role in the processing of the amyloid-␤ protein precursor (A␤PP), as well as in the autophagy removal of proteins susceptible to aggregation from the brains of patients with AD and probably also in ischemic neurodegeneration [17,18]. Regulation of the expression of beclin 1 in the brain tissue of patients with AD at the transcriptional level has not been fully elucidated.…”

Advancements in AAV-mediated Gene Therapy for Pompe Disease

“…Thus, the autophagy-lysosomal pathway plays a crucial role in the removal of worn-out organelles and toxic components as well as in cellular adaptation to various stresses and starvation. Dysfunctional autophagy has been associated with a range of pathologies including cancer, neurodegeneration, metabolic and cardiac diseases, and not surprisingly, LSDs including Pompe disease [56,57]. The process is particularly important for the survival and stress adaptation of post-mitotic cells like neurons or muscle cells that are most affected in Pompe disease.…”

Molecular Pathogenicity of Enteroviruses Causing Neurological Disease

“…As a result, EVinduced dysregulation of host autophagy can have a directly deleterious effect on cells due to the loss of autophagy's normal protective functions . Neurons are post-mitotic cells that are more prone to the accumulation of toxic metabolic byproducts than dividing cells, which experience higher regeneration of cytoplasm and organelles (Lee, 2012;Meng et al, 2019). Because of the high energy demands of the brain, neurons are sensitive to starvation, which is known to initiate autophagy through the mammalian target of rapamycin (mTOR) pathway (Heras-Sandoval et al, 2019).…”