Autophagy

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Key concepts in ALS

Autophagy allows the orderly degradation and recycling of cellular components.

  • In macroautophagy, targeted cytoplasmic constituents are isolated from the rest of the cell within a double-membraned vesicle known as an autophagosome.
  • The autophagosome eventually fuses with lysosomes and the contents are degraded and recycled.
  • Three forms of autophagy are also commonly described: macroautophagy, microautophagy and chaperone-mediated autophagy (CMA).
  • In disease, autophagy has been seen as an adaptive response to stress, which promotes survival, whereas in other cases it appears to promote cell death and morbidity.
  • In the extreme case of starvation, the breakdown of cellular components promotes cellular survival by maintaining cellular energy levels.

The most prevalent pathological features of many neurodegenerative diseases are the aggregation of misfolded proteins and the loss of certain neuronal populations. Autophgy, as major intracellular machinery for degrading aggregated proteins and damaged organelles, has been reported to be involved in the occurance of pathological changes in many neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. In this review, we summarized most recent research progress in this topic and provide a new perspective regarding autophagy regulation on the pathogenesis of neurodegenerative diseases. Finally, we further discussed the signaling molecules in autophagy-related pathways as therapeutic targets for the treatment of these diseases. ' [1]

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders that share genetic risk factors and pathological hallmarks. Intriguingly, these shared factors result in a high rate of comorbidity of these diseases in patients. Intracellular protein aggregates are a common pathological hallmark of both diseases. Emerging evidence suggests that impaired RNA processing and disrupted protein homeostasis are two major pathogenic pathways for these diseases. Indeed, recent evidence from genetic and cellular studies of the etiology and pathogenesis of ALS-FTD has suggested that defects in autophagy may underlie various aspects of these diseases. In this review, we discuss the link between genetic mutations, autophagy dysfunction, and the pathogenesis of ALS-FTD. Although dysfunction in a variety of cellular pathways can lead to these diseases, we provide evidence that ALS-FTD is, in many cases, an autophagy disease. [2]

References[edit]

  1. Guo et al.: Autophagy in Neurodegenerative Diseases: Pathogenesis and Therapy. Brain Pathol. 2017;. PMID: 28703923. DOI. The most prevalent pathological features of many neurodegenerative diseases are the aggregation of misfolded proteins and the loss of certain neuronal populations. Autophgy, as major intracellular machinery for degrading aggregated proteins and damaged organelles, has been reported to be involved in the occurance of pathological changes in many neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. In this review, we summarized most recent research progress in this topic and provide a new perspective regarding autophagy regulation on the pathogenesis of neurodegenerative diseases. Finally, we further discussed the signaling molecules in autophagy-related pathways as therapeutic targets for the treatment of these diseases. This article is protected by copyright. All rights reserved.
  2. Deng et al.: Is amyotrophic lateral sclerosis/frontotemporal dementia an autophagy disease?. Mol Neurodegener 2017;12:90. PMID: 29282133. DOI. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders that share genetic risk factors and pathological hallmarks. Intriguingly, these shared factors result in a high rate of comorbidity of these diseases in patients. Intracellular protein aggregates are a common pathological hallmark of both diseases. Emerging evidence suggests that impaired RNA processing and disrupted protein homeostasis are two major pathogenic pathways for these diseases. Indeed, recent evidence from genetic and cellular studies of the etiology and pathogenesis of ALS-FTD has suggested that defects in autophagy may underlie various aspects of these diseases. In this review, we discuss the link between genetic mutations, autophagy dysfunction, and the pathogenesis of ALS-FTD. Although dysfunction in a variety of cellular pathways can lead to these diseases, we provide evidence that ALS-FTD is, in many cases, an autophagy disease.