A Chinese patient with the clinical features of Parkinson’s disease contains a single copy of octarepeat deletion in PRNP case report

Shi, Qi; Shen, Xiaojing; Gao, Liping; Xiao, Kang; Zhou, Wei; Wang, Yuan; Cao, Chen; Dong, Xiaoping

doi:10.1080/19336896.2021.1946376

Cited by 3 publications

(1 citation statement)

References 23 publications

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“…[37] This is further supported by several clinical studies showing truncation of the OPR region is associated with clinical disease phenotypes similar to those of Creutzfeld-Jakob disease and Parkinson's disease, along with rapidly progressive dementia. [38][39][40] Thus, although loss of OPR regions may blunt the self-assembly and neurotoxic effects of PrP Sc , it does not significantly influence the susceptibility of PrP C to convert to the pathogenic, infectious PrP Sc form and its consequent disease lethality.…”

Section: Opr Truncationmentioning

confidence: 99%

The manifold role of octapeptide repeats in prion protein assembly

Guadagno

Medina

2023

Peptide Science

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Prion protein misfolding is associated with fatal neurodegenerative disorders such as kuru, Creutzfeldt–Jakob disease, and several animal encephalopathies. While the C‐terminal 106–126 peptide has been well studied for its role in prion replication and toxicity, the octapeptide repeat (OPR) sequence found within the N‐terminal domain has been relatively under explored. Recent findings that the OPR has both local and long‐range effects on prion protein folding and assembly, as well as its ability to bind and regulate transition metal homeostasis, highlights the important role this understudied region may have in prion pathologies. This review attempts to collate this knowledge to advance a deeper understanding on the varied physiologic and pathologic roles the prion OPR plays, and connect these findings to potential therapeutic modalities focused on OPR‐metal binding. Continued study of the OPR will not only elucidate a more complete mechanistic model of prion pathology, but may enhance knowledge on other neurodegenerative processes underlying Alzheimer's, Parkinson's, and Huntington's diseases.

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Section: Opr Truncationmentioning

confidence: 99%

The manifold role of octapeptide repeats in prion protein assembly

Guadagno

Medina

2023

Peptide Science

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The Impact of the Blood–Brain Barrier and Its Dysfunction in Parkinson’s Disease: Contributions to Pathogenesis and Progression

Khalid Iqbal,

Khan,

Hifsa

et al. 2024

ACS Omega

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Parkinson's disease (PD) is a brain disorder in which neuronal cells responsible for the release of dopamine, a neurotransmitter that controls movement, are degenerated or impaired in the substantia nigra and basal ganglia. The disease typically affects people over the age of 5 and presents with a variety of motor and nonmotor dysfunctions, which are unique to each person. The impairment of the blood−brain barrier (BBB) and blood retinal barrier (BRB) due to age-related causes such as weakness of tight junctions or rare genetic factors allows several metabolic intermediates to reach and accumulate inside neurons such as Lewy bodies and α-synuclein, disrupting neuronal homeostasis and leading to genetic and epigenetic changes, e.g., damage to the DNA repair system. This perspective highlights the importance of blood barriers, such as the BBB and BRB, in the progression of PD, as the aggregation of Lewy bodies and αsynuclein disrupts neuronal homeostasis. Genetic and epigenetic factors, neuroinflammation, oxidative stress, and mitochondrial dysfunction play crucial roles in the progression of the disease. The implications of these findings are significant; identifying synaptic dysfunction could lead to earlier diagnosis and treatment, while developing targeted therapies focused on preserving synaptic function may slow or halt disease progression. Understanding the various genetic forms of PD could enable more personalized medicine approaches, and using patient-derived midbrain neurons for research may improve the accuracy of PD models due to the implications of an impaired BBB.

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Prion Mutations in Republic of Republic of Korea, China, and Japan

Kim

Shim

Bagyinszky

et al. 2022

IJMS

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Prion gene (PRNP) mutations are associated with diverse disease phenotypes, including familiar Creutzfeldt–Jakob Disease (CJD), Gerstmann–Sträussler–Scheinker disease (GSS), and fatal familial insomnia (FFI). Interestingly, PRNP mutations have been reported in patients diagnosed with Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease, and frontotemporal dementia. In this review, we describe prion mutations in Asian countries, including Republic of Republic of Korea, China, and Japan. Clinical phenotypes and imaging data related to these mutations have also been introduced in detail. Several prion mutations are specific to Asians and have rarely been reported in countries outside Asia. For example, PRNP V180I and M232R, which are rare in other countries, are frequently detected in Republic of Korea and Japan. PRNP T188K is common in China, and E200K is significantly more common among Libyan Jews in Israel. The A117V mutation has not been detected in any Asian population, although it is commonly reported among European GSS patients. In addition, V210I or octapeptide insertion is common among European CJD patients, but relatively rare among Asian patients. The reason for these differences may be geographical or ethical isolation. In terms of clinical phenotypes, V180I, P102L, and E200K present diverse clinical symptoms with disease duration, which could be due to other genetic and environmental influences. For example, rs189305274 in the ACO1 gene may be associated with neuroprotective effects in cases of V180I mutation, leading to longer disease survival. Additional neuroprotective variants may be possible in cases featuring the E200K mutation, such as KLKB1, KARS, NRXN2, LAMA3, or CYP4X1. E219K has been suggested to modify the disease course in cases featuring the P102L mutation, as it may result in the absence of prion protein-positive plaques in tissue stained with Congo red. However, these studies analyzed only a few patients and may be too preliminary. The findings need to be verified in studies with larger sample sizes or in other populations. It would be interesting to probe additional genetic factors that cause disease progression or act as neuroprotective factors. Further studies are needed on genetic modifiers working with prions and alterations from mutations.

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A Chinese patient with the clinical features of Parkinson’s disease contains a single copy of octarepeat deletion in PRNP case report

Cited by 3 publications

References 23 publications

The manifold role of octapeptide repeats in prion protein assembly

The manifold role of octapeptide repeats in prion protein assembly

The Impact of the Blood–Brain Barrier and Its Dysfunction in Parkinson’s Disease: Contributions to Pathogenesis and Progression

Prion Mutations in Republic of Republic of Korea, China, and Japan

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