Recent advances in novel mutation genes of Parkinson's disease

Yang, Jie; Wu, Xinyu; Song, Yuning

doi:10.1007/s00415-023-11781-4

Cited by 3 publications

(3 citation statements)

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“…In a comprehensive analysis using a large population-based twin registry, the heritability of PD for an age of diagnosis of less than 50 years was estimated at 0.83 ( Goldman et al, 2019 ; Uwishema et al, 2022 ). Recently, genome-wide analyses of clinical cases of PD patients have identified a new set of PD-associated genes, including ANK2, DNAH1, and STAB1 ( Yang et al, 2023 ).…”

Section: Parkinson’s Diseasementioning

confidence: 99%

Potential role of N6-methyladenosine modification in the development of Parkinson’s disease

Zhou,

Han,

Hou

2023

Front. Cell Dev. Biol.

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N6-methyladenosine (m6A) represents the most abundant modification of messenger RNA (mRNA) and is regulated by methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers). A dynamic modification process is implicated in nearly every critical stage of RNA metabolism, including mRNA stability, transcription, translation, splicing, nuclear export, and decay. Notably, m6A methylation is significantly enriched in the brain and has recently been shown to be associated with neurodevelopmental disorders and the development of Parkinson’s disease (PD). In this review, we summarize the proteins involved in the process of m6A modification and elucidate the emerging role of m6A modification in PD, which could illuminate alternative strategies for the prevention and treatment of PD.

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Section: Parkinson’s Diseasementioning

confidence: 99%

Potential role of N6-methyladenosine modification in the development of Parkinson’s disease

Zhou,

Han,

Hou

2023

Front. Cell Dev. Biol.

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“…Parkinson's Disease (PD) is becoming increasingly prevalent in our ageing population and is the most common neurodegenerative movement disorder, affecting 1-2% of people aged over 65, with an estimated > 6.1 million people affected worldwide 1 .There has been a wealth of research into genetic and proteomic changes affected by PD [2][3][4][5] , however it is becoming more and more apparent that dysregulated lipid pathways also play a role in the aetiology of the disease [6][7][8][9] . Importantly, it has been observed that α-synuclein aggregation is affected by lipids 9 and that α-synuclein inclusions have a high lipid content 10 .…”

Section: Graphical Abstract Introductionmentioning

confidence: 99%

“…To expand on the knowledge of lipid expression in the human brain, we have profiled multiple brain regions in sporadic early-to mid-stage PD (Braak stage 3-4), and late-stage PD (Braak stage [5][6], exploring how the lipid profile changes across eight brain regions in relation to age and disease, and correlated these findings with proteomics data in a multi-omic approach. We applied targeted lipid panels consisting of the main non-cholesterol lipids that are abundant in the brain, including sphingolipids, glycosphingolipids, and phospholipids as well as their deacylated lyso-forms.…”

Section: Graphical Abstract Introductionmentioning

confidence: 99%

Multi-Omic Analysis Reveals Lipid Dysregulation Associated with Mitochondrial Dysfunction in Parkinson’s Disease Brain

Hällqvist,

Toomey,

Pinto

et al. 2024

Preprint

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Parkinson's Disease (PD) is an increasingly prevalent condition within the aging population. PD can be attributed to rare genetic mutations, but most cases are sporadic where the gene-environment interactions are unknown/likely contributory. Age related dysregulation of the glycosphingolipid degradation pathway has been implicated in the development of PD, however, our understanding of how brain lipids vary across different regions of the brain, with age and in disease stages, remains limited. In this study we profiled several phospho- and sphingolipid classes in eight distinct regions of the human brain and investigated the association of lipids with a spatio-temporal pathology gradient, utilising PD samples from early, mid, and late stages of the disease. We performed high-precision tissue sampling in conjunction with targeted LC-MS/MS and applied this to post-mortem samples from PD and control subjects. The lipids were analysed for correlations with untargeted proteomics and mitochondrial activity data, in a multi-omics approach. We concluded that the different brain regions demonstrated their own distinct profiles and also found that several lipids were correlated with age. The strongest differences between PD and controls were identified in ganglioside, sphingomyelin and n-hexosylceramides. Sphingomyelin was also found to correlate with several proteins implicated in Parkinson's disease pathways. Mitochondrial activity was correlated with the levels of several lipids in the putamen region. Finally, we identified a gradient corresponding to Braak's disease spread across the brain regions, where the areas closer to the brainstem/substantia nigra showed alterations in PC, LPC and glycosphingolipids, while the cortical regions showed changes in glycosphingolipids, specifically gangliosides, HexCer and Hex2Cer.

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