Compromised autophagy and neurodegenerative diseases

@article{Menzies2015CompromisedAA,
  title={Compromised autophagy and neurodegenerative diseases},
  author={Fiona M Menzies and Angeleen Fleming and David C. Rubinsztein},
  journal={Nature Reviews Neuroscience},
  year={2015},
  volume={16},
  pages={345-357}
}
Most neurodegenerative diseases that afflict humans are associated with the intracytoplasmic deposition of aggregate-prone proteins in neurons and with mitochondrial dysfunction. Autophagy is a powerful process for removing such proteins and for maintaining mitochondrial homeostasis. Over recent years, evidence has accumulated to demonstrate that upregulation of autophagy may protect against neurodegeneration. However, autophagy dysfunction has also been implicated in the pathogenesis of… Expand
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References

SHOWING 1-10 OF 194 REFERENCES
Autophagy and neurodegeneration.
TLDR
How certain neurodegenerative diseases may be associated with impaired autophagy and how this may affect pathology is considered and some of the signaling pathways that may be amenable to therapeutic targeting for these goals are described. Expand
Chaperone-mediated autophagy: roles in neurodegeneration
TLDR
The therapeutic potential of targeting CMA in the treatment of neurodegenerative diseases is discussed and several new mechanisms by which CMA function may be involved in the regulation of factors critical for neuronal viability and homeostasis are revealed. Expand
Control of autophagy as a therapy for neurodegenerative disease
TLDR
The ways in which dysfunctions at multiple stages in the autophagic pathways contribute to numerous neurological disorders are highlighted through the use of examples of Mendelian and complex conditions, including Alzheimer disease, Parkinson disease and forms of motor neuron disease. Expand
The roles of intracellular protein-degradation pathways in neurodegeneration
TLDR
Improving macroautophagy with drugs such as rapamycin could offer a tractable therapeutic strategy for a number of late-onset neurodegenerative diseases. Expand
Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy
TLDR
The effects of autophagy stimulation by trehalose in a transgenic mouse model of tauopathy, the human mutant P301S tau mouse, are assessed using biochemical and immunohistochemical analyses to provide direct evidence in favour of the degradation of tAU aggregates by autophagic. Expand
Calpain inhibition mediates autophagy-dependent protection against polyglutamine toxicity
TLDR
It is demonstrated, in Drosophila, that calpain knockdown protects against the aggregation and toxicity of proteins, like mutant huntingtin, in an autophagy-dependent fashion, and overexpression of the calpain inhibitor, calpastatin, increases autophagosome levels and is protective in a mouse model of Huntington’s disease. Expand
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
TLDR
The results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration. Expand
Impaired proteolysis underlies autophagic dysfunction in Niemann-Pick type C disease.
TLDR
Inhibition of autophagy reduces cholesterol storage and restores normal lysosomal proteolysis in NPC1-deficient cells, supporting a model in which activation of the autophagic pathway promotes disease pathogenesis. Expand
Disruption and therapeutic rescue of autophagy in a human neuronal model of Niemann Pick type C1.
TLDR
It is suggested that neurons are especially sensitive to lysosomal cholesterol accumulation because of autophagy disruption and accumulation of fragmented mitochondria, thus defining a new route to effective drug development for NPC1 disease. Expand
Impaired Degradation of Mutant α-Synuclein by Chaperone-Mediated Autophagy
TLDR
It is found that wild-type α-synuclein was selectively translocated into lysosomes for degradation by the chaperone-mediated autophagy pathway, which may underlie the toxic gain-of-function by the A53T and A30P mutants. Expand
...
1
2
3
4
5
...