6) The knockout of essential genes from the autophagic cascade entails a major cellular dysfunction due to accumulating, dysfunctional mitochondria (and perhaps other organelles and protein aggregates).
Evidence has been accumulated that dysfunction of Tor results in impairment of overall protein synthesis[1].
The activation of astrocytes towards oxidative stress generation in chronic neuroinflammation supports the hypothesis that these cells are partially responsible for the accumulated neuronal dysfunction and damage over the course of the disease.
Therefore, the late onset neurological symptoms and neurodegeneration appear to be a consequence of accumulating neuronal dysfunction due to protein deficiency from the outset.
Nothing short of a total overhaul of the constitution will repair the years of accumulated damage and dysfunction, he believes.
"I'm really optimistic that once we get the dysfunction accumulated during years of neglect straightened out, I could see this becoming a really creative focal point for lots of people," Mr. Frost said.
Increasing evidences have accumulated that endothelial dysfunction is involved in the pathogenesis of hypertension.
The authors concluded upon "a role for inflammatory cells in the initiation of mitochondrial DNA damage, which when accumulated causes respiratory dysfunction, fibre atrophy and ultimately degeneration of muscle fibres" [ 85].
A leading hypothesis for these outcomes has been that the patients in the studies were too far down the pathologic cascade when the neuronal damage and synaptic dysfunction accumulated to an irreversible degree.
Accumulated mhtt causes the dysfunction of astrocytes, particularly in relation to glutamate uptake, since it decreases the expression of glutamate transporters.
During the last decade, a large body of evidence has been accumulated on participation of mitochondrial dysfunctions in pathogeneses of practically all major pathologies in human [ 1, 8, 159, 160].
