Australian Parkinson’s Genetics Study (APGS): pilot (n=1532)

Bivol, Svetlana; Mellick, George D.; Gratten, Jacob; Parker, Richard; Mulcahy, Aoibhe; Mosley, Philip; Poortvliet, Peter C.; Campos, Adrián I.; Mitchell, Brittany; García-Marín, Luis M.; Cross, Sheree E.; Ferguson, Mary Ellen; Lind, Penelope A.; Loesch, Danuta Z.; Visscher, Peter M.; Medland, Sarah E.; Scherzer, Clemens R.; Martin, Nicholas G.; Rentería, Miguel E.

doi:10.1136/bmjopen-2021-052032

Cited by 5 publications

(3 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Depression is a major non-motor symptom of PD [17]. Autopsies of patients with PD indicating protein accumulation and neurodegenerative changes show that disruption of liposome-mediated degradation blocks lysosomal clearance of macromolecules and damaged organelles in the brain [18].…”

Section: Discussionmentioning

confidence: 99%

β-Asarone Promotes Autophagy by Inhibiting the PI3K/Akt/mTOR Pathway in a Rat Model of Depression in Parkinson’s Disease

Wang,

Zhang

et al. 2022

Preprint

View full text Add to dashboard Cite

Depression in Parkinson’s disease (DPD) is a major non-motor symptom of Parkinson’s disease (PD), and is accompanied by monoamine neurotransmitter degradation in DPD rats. Autophagy is neuroprotective because it helps degrade abnormal deposition of α-synuclein (α-syn). The PI3K/Akt/mTOR pathway is a key autophagy pathway. β-Asarone, derived from Acorus tatarinowii Schott, has anti-PD and anti-depression effects. This study aimed to investigate the mechanism of action of β-asarone in the treatment of DPD model rats. We found that oral administration of β-asarone (7.5, 15, and 30 mg/kg) for 4 weeks increased dopamine, L-DOPA (levodopa; L-3,4-dihydroxyphenylalanine), and serotonin levels in the midbrain and decreased α-syn levels in DPD model rats compared with model group. As the neurotransmitter levels changed, the expression of Beclin-1 increased while that of p62 decreased in β-asarone-treated DPD rats compared with that in controls. Transmission electron microscopy (TEM) showed that β-asarone treatment also improved the number of autophagosomes and decreased mitochondrial damage in the striatum compared with that in untreated animals. These results suggest that β-asarone activates autophagy. Furthermore, western blotting and transmission electron microscopy analyses revealed that the PI3K/Akt/mTOR pathway played an important role in β-asarone treatment-induced activation of autophagy. Furthermore, β-asarone increased the levels of Beclin-1 protein and reduced the expression of p62, p-PI3K, p-AKT, and p-mTOR in the hippocampus. Lastly, transmission electron microscopy results demonstrated that the β-asarone-treated animals displayed abundant autophagosomes in the prefrontal cortex. These findings suggest that β-asarone exerts neuroprotective effects in this DPD model via the promotion of autophagy, and may be an effective therapeutic agent for DPD treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

β-Asarone Promotes Autophagy by Inhibiting the PI3K/Akt/mTOR Pathway in a Rat Model of Depression in Parkinson’s Disease

Wang,

Zhang

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…For instance, TwinsMX was built to be comparable to the Australian ( 79 ) and UK ( 80 ) Twins Registries. At the same time, MEX-PD is akin to the newly established Australian Parkinson's Genetics Study ( 81 ) and the Latin American Research Consortium on the Genetics of Parkinson's Disease ( 82 ).…”

Section: Methodsmentioning

confidence: 99%

Building national patient registries in Mexico: insights from the MexOMICS Consortium

Reyes-Pérez,

Hernández-Ledesma,

Román-López

et al. 2024

Front. Digit. Health

View full text Add to dashboard Cite

ObjectiveTo introduce MexOMICS, a Mexican Consortium focused on establishing electronic databases to collect, cross-reference, and share health-related and omics data on the Mexican population.MethodsSince 2019, the MexOMICS Consortium has established three electronic-based registries: the Mexican Twin Registry (TwinsMX), Mexican Lupus Registry (LupusRGMX), and the Mexican Parkinson's Research Network (MEX-PD), designed and implemented using the Research Electronic Data Capture web-based application. Participants were enrolled through voluntary participation and on-site engagement with medical specialists. We also acquired DNA samples and Magnetic Resonance Imaging scans in subsets of participants.ResultsThe registries have successfully enrolled a large number of participants from a variety of regions within Mexico: TwinsMX (n = 2,915), LupusRGMX (n = 1,761) and MEX-PD (n = 750). In addition to sociodemographic, psychosocial, and clinical data, MexOMICS has collected DNA samples to study the genetic biomarkers across the three registries. Cognitive function has been assessed with the Montreal Cognitive Assessment in a subset of 376 MEX-PD participants. Furthermore, a subset of 267 twins have participated in cognitive evaluations with the Creyos platform and in MRI sessions acquiring structural, functional, and spectroscopy brain imaging; comparable evaluations are planned for LupusRGMX and MEX-PD.ConclusionsThe MexOMICS registries offer a valuable repository of information concerning the potential interplay of genetic and environmental factors in health conditions among the Mexican population.

show abstract

“…Although NDDs are classified primarily based on their clinical features, the molecular hallmarks of neural loss and their anatomic distribution are often used to identify similarities and differences in their nosology. For example, PD is characterised by the progressive loss of dopaminergic neurons in the substantia nigra, and the appearance of intracellular inclusions called Lewy bodies [3]. In contrast, the molecular pathogenesis of AD is primarily driven by the accumulation of neurofibrillary tangles and amyloid plaques in the entorhinal cortex, hippocampus, and basal forebrain [4].…”

Section: Introductionmentioning

confidence: 99%

Impact of genetic predisposition to late-onset neurodegenerative diseases on early life outcomes and brain structure

Ogonowski,

García-Marín,

Fernando

et al. 2024

Transl Psychiatry

Self Cite

View full text Add to dashboard Cite

Most patients with late-onset neurodegenerative diseases such as Alzheimer’s and Parkinson’s have a complex aetiology resulting from numerous genetic risk variants of small effects located across the genome, environmental factors, and the interaction between genes and environment. Over the last decade, genome-wide association studies (GWAS) and post-GWAS analyses have shed light on the polygenic architecture of these diseases, enabling polygenic risk scores (PRS) to estimate an individual’s relative genetic liability for presenting with the disease. PRS can screen and stratify individuals based on their genetic risk, potentially years or even decades before the onset of clinical symptoms. An emerging body of evidence from various research studies suggests that genetic susceptibility to late-onset neurodegenerative diseases might impact early life outcomes, including cognitive function, brain structure and function, and behaviour. This article summarises recent findings exploring the potential impact of genetic susceptibility to neurodegenerative diseases on early life outcomes. A better understanding of the impact of genetic susceptibility to neurodegenerative diseases early in life could be valuable in disease screening, detection, and prevention and in informing treatment strategies before significant neural damage has occurred. However, ongoing studies have limitations. Overall, our review found several studies focused on APOE haplotypes and Alzheimer’s risk, but a limited number of studies leveraging polygenic risk scores or focused on genetic susceptibility to other late-onset conditions.

show abstract

Australian Parkinson’s Genetics Study (APGS): pilot (n=1532)

Cited by 5 publications

References 89 publications

β-Asarone Promotes Autophagy by Inhibiting the PI3K/Akt/mTOR Pathway in a Rat Model of Depression in Parkinson’s Disease

β-Asarone Promotes Autophagy by Inhibiting the PI3K/Akt/mTOR Pathway in a Rat Model of Depression in Parkinson’s Disease

Building national patient registries in Mexico: insights from the MexOMICS Consortium

Impact of genetic predisposition to late-onset neurodegenerative diseases on early life outcomes and brain structure

Contact Info

Product

Resources

About