https://pubmed.ncbi.nlm.nih.gov/27188817/
ASO v RNAi v siRNA
QT:{{”
how a specific toxic conformation might be favoured
within the expanded polyQ of monomeric HTT exon1
is unclear37,47. More-complex conformational effects in
monomeric HTT exon1 linked to polyQ repeat length
are formally possible but challenging to establish37,49. By
contrast, the widely reported ability of HTT exon1 to
readily form a variety of aggregated structures presents
an array of plausible candidates that might mediate toxicity (see below)37. This aggregation links Huntington
disease to other neurodegenerative diseases that feature
a protein aggregation component, including Alzheimer
disease, Parkinson disease, amyotrophic lateral sclerosis
and spongiform encephalopathies.
…
bind to HTT mRNA selectively and target it for degradation
by cellular mechanisms. When the agent is a short
interfering RNA (siRNA) or microRNA, the HTT
mRNA is degraded by cytoplasmic RNA-induced silencing
complex (RISC) — a process known as RNA interference
(RNAi). Alternatively, a single-stranded modified
DNA molecule or antisense oligonucleotide (ASO) can
be used to direct the transcript for degradation by
nuclear ribonuclease H.
“}}
Bates, G. P., Dorsey, R., Gusella, J. F., Hayden, M. R., Kay, C., Leavitt, B. R., Nance, M., Ross, C. A., Scahill, R. I., Wetzel, R., Wild, E. J., & Tabrizi, S. J. (2015). Huntington disease. Nature Reviews Disease Primers, 1(1), 15005.
https://doi.org/10.1038/nrdp.2015.5
from G search {{
”
Yes, amyloid fibrils in Huntington’s disease (HD) contain a specific protein—the mutated huntingtin (Htt) protein. These fibrils are formed specifically from the N-terminal exon 1 fragment of the mutant protein, which contains an expanded polyglutamine (polyQ) tract that forms the amyloid core.
….
Although they contain the mutant protein, the amyloid fibrils in HD are distinct from those in Alzheimer’s (A
) or Parkinson’s (
-synuclein) diseases.
”
}}
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