Parkinson’s Disease (PD) is a widespread severe neurodegenerative disease that is characterized by pronounced deficiency of the dopaminergic system and disruption of the function of other neuromodulator systems. Although heritable genetic factors contribute significantly to PD pathogenesis, only a small percentage of sporadic cases of PD can be explained using known genetic risk factors. Due to that, it could be inferred that changes in gene expression could be important for explaining a significant percentage of PD cases. One of the ways to investigate such changes, while minimizing the effect of genetic factors on experiment, are the study of PD discordant monozygotic twins. In the course of the analysis of transcriptome data obtained from IPSC and NPCs, 20 and 1906 differentially expressed genes were identified respectively. We have observed an overexpression of TNF in NPC cultures, derived from twin with PD. Through investigation of gene interactions and gene involvement in biological processes, we have arrived to a hypothesis that TNF could play a crucial role in PD-related changes occurring in NPC derived from twins with PD, and identified INHBA, WNT7A and DKK1 as possible downstream effectors of TNF.
ANXA2 is a multifunctional member of the annexin protein family, implicated in vesicular transport, antioxidant defense, and actin remodeling. Its role in oncogenesis is actively investigated, notably in glioblastoma, astrocytoma, and breast cancer. However, a growing body of literature explores ANXA2’s involvement in neurodegenerative processes. The evidence suggests a potential contribution of ANXA2 to the pathogenesis of primary and secondary tauopathies, as well as Parkinson’s disease. It is crucial to note that the majority of these findings are correlative and necessitate further experimental validation. This review therefore presents a comprehensive analysis of data pertaining to ANXA2’s involvement in various cellular processes, the disruption of which contributes to neurological pathologies.
Parkinson’s disease (PD) is characterized by a long prodromal period, during which patients often have sleep disturbances. The histaminergic system and circadian rhythms play an important role in the regulation of the sleep–wake cycle. Changes in the functioning of these systems may be involved in the pathogenesis of early stages of PD and may be age-dependent. Here, we have analyzed changes in the expression of genes associated with the regulation of the sleep–wake cycle (Hnmt, Hrh1, Hrh3, Per1, Per2, and Chrm3) in the substantia nigra (SN) and striatum of normal male mice of different ages, as well as in young and adult male mice with an MPTP-induced model of the early symptomatic stage (ESS) of PD. Age-dependent expression analysis in normal mouse brain tissue revealed changes in Hrh3, Per1, Per2, and Chrm3 genes in adult mice relative to young mice. When gene expression was examined in mice with the MPTP-induced model of the ESS of PD, changes in the expression of all studied genes were found only in the SN of adult mice with the ESS model of PD. These data suggest that age is a significant factor influencing changes in the expression of genes associated with sleep–wake cycle regulation in the development of PD.
1 September 2023 in Molecular Genetics, Microbiology and Virology
The Annexin 2 protein (ANXA2) encoded by the ANXA2 gene performs a number of biological functions that are primarily related to cellular transport. An impa
Parkinson’s disease (PD) is one of the most common human neurodegenerative diseases. Belated diagnoses of PD and late treatment are caused by its elongated prodromal phase. Thus, searching for new candidate genes participating in the development of the pathological process in the early stages of the disease in patients who have not yet received therapy is relevant. Changes in mRNA and protein levels have been described both in the peripheral blood and in the brain of patients with PD. Thus, analysis of changes in the mRNA expression in peripheral blood is of great importance in studying the early stages of PD. This work aimed to analyze the changes in MEF2C, SLC22A4, P2RY12, and LRRN3 gene expression in the peripheral blood of patients in the early stages of PD. We found a statistically relevant and PD-specific change in the expression of the LRRN3 gene, indicating a disruption in the processes of neuronal regeneration and the functioning of synapses. The data obtained during the study indicate that this gene can be considered a potential biomarker of the early stages of PD.
22 April 2024 in Molecular Genetics Microbiology and Virology (Russian version)
INTRODUCTION The Danio rerio (D. rerio) is one of the advanced targets for modelling pathological conditions. A large amount of such work in this case is carried out at the transcriptomic level. Transcriptomic studies require the use of stable housekeeping genes (HKG), so we selected candidate HKG and analyzed their stability in D. rerio under normal conditions. MATHERIAL AND METHODS The work was carried out using D. rerio (line AB) whose embryos were sampled at three time points: hatching stage (2 days post-fertilisation, dpf), early larvae stages (5 dpf and 9 dpf). The expression levels of HKGs were analyzed using real-time PCR. Further analysis of the obtained Ct results was performed in RefFinder software. RESULTS Different HKGs are suitable for assessing gene expression changes at different developmental stages of D.rerio. aars1 and polr2f is the optimal pair of HKGs at the hatching stage (2 dpf), aars1 and psmd6 are most suitable for the early larvae stage (5 dpf), bcat2 and actb1 are most suitable for 9 dpf. During the transcriptomic studies at several developmental stages simultaneously, it is necessary to use a single selected pair of HKGs for all investigated stages of development of D.rerio: aars1 and lsm12b. CONCLUSION According to the data obtained, aars1 and lsm12b are the most stable HKGs for all studied early developmental stages of D.rerio. In addition, we have shown for the first time that aars1 is the most stable HKG for the early stages of development. The second most stable HKG is lsm12b. Our data about the stability of the lsm12b gene are consistent with previously published data.