Inherited prion disease A117V is not simply a proteinopathy
but produces prions transmissible to transgenic mice expressing homologous prion protein.
The decrease in dopamine transporter (DAT) uptake is an effective imaging marker that indicates the development of iRBD to a-synaptic proteinopathy
. A study has found that when healthy people developed subclinical RBD, there was a progressive decrease in striatal DAT. The reduction of DAT in the striatum and putamen was associated with a high risk of a-synaptic proteinopathy
. However, the glucose and dopamine metabolisms are not specific for reflecting cognitive function.
HD is a unique neurodegenerative proteinopathy
, insofar as autophagy is dysfunctional, and wild-type HTT also appears to play several roles in regulating the dynamics of autophagy (54).
AD is caused by progressive neurodegeneration in the medial temporal lobe, hippocampus formation, and other brain areas with synergistic amyloid and tau proteinopathy
Kimonis, "Rapamycin and chloroquine: the in vitro and in vivo effects of autophagy-modifying drugs show promising results in valosin containing protein multisystem proteinopathy
," Plos One, vol.
Gitler, "A yeast TDP-43 proteinopathy
model: Exploring the molecular determinants of TDP-43 aggregation and cellular toxicity," Proceedings of the National Acadamy of Sciences of the United States of America, vol.
Thus, downregulation of TDP-43 strongly correlates with the reduced steady-state levels of these transcripts, providing a potential mechanism for neuronal vulnerability in TDP-43 proteinopathy
. Collectively, deregulation of TDP-43 RNA targets through the loss of TDP-43 function could at least in part contribute to synaptic functions and ALS-FTD disease pathogenesis.
Considering these aspects, we hypothesized that widespread TDP-43 and UCH-L1 proteinopathy
may underlie multifocal neuronal dysfunction that contributes to complex nonmotor phenotypes in autism, including cognitive impairment with prominent frontal executive dysfunction and extrapyramidal signs.
As illustrated in Figure 1, A through F, neuropathologic examination revealed 4 common pathologies of aging rather than AD neuropathology in this patient with dementia, namely: (1) a TDP-43 proteinopathy
involving limbic structures without HS, that is, CARTS; (2) multifocal largeand small-vessel vascular brain injury; (3) Braak stage II--III without amyloid deposition, consistent with PART; and (4) the non-AD tauopathy of argyrophilic grains.
and Motor Neuron Disease in Chronic Traumatic Encephalopathy.
Osinska et al., "Enhanced autophagy ameliorates cardiac proteinopathy
," Journal of Clinical Investigation, vol.
Wang et al., "Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy
and ALS," Nature, vol.