Neurochemical and Morphological Changes in the Microstructures of the Compact Part of the Substantia Nigra of the Human Brain in Aging and Parkinson’s Disease (Literature Review)

Salkov, V N; Khudoerkov, R. M.

doi:10.1134/s207905701902019x

Cited by 2 publications

(2 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The nigrostriatal dopaminergic pathway connects the substantia nigra pars compacta (SNc) with the dorsal striatum, forms part of the extrapyramidal system, and plays a central role in motor control (Tepper and Lee, 2007;Tritsch et al, 2012). Selective loss of dopaminergic neurons in the SNc represents a cardinal pathological feature of Parkinson's disease (PD), and consequent dopamine depletion in the striatum results in marked motor deficits, including tremors, rigidity, hypokinesia and postural imbalance (Salkov and Khudoerkov, 2018).…”

Section: Introductionmentioning

confidence: 99%

KTN1 Variants Underlying Putamen Gray Matter Volumes and Parkinson’s Disease

et al. 2020

View full text Add to dashboard Cite

Background: Selective loss of dopaminergic neurons and diminished putamen gray matter volume (GMV) represents a central feature of Parkinson's disease (PD). Recent studies have reported specific effects of kinectin 1 gene (KTN1) variants on the putamen GMV. Objective: To examine the relationship of KTN1 variants, KTN1 mRNA expression in the putamen and substantia nigra pars compacta (SNc), putamen GMV, and PD. Methods: We examined the associations between PD and a total of 1847 imputed KTN1 single nucleotide polymorphisms (SNPs) in one discovery sample [2,000 subjects with PD vs. 1,986 healthy controls (HC)], and confirmed the nominally significant associations (p < 0.05) in two replication samples (900 PD vs. 867 HC, and 940 PD vs. 801 HC, respectively). The regulatory effects of risk variants on the KTN1 mRNA expression in putamen and SNc and the putamen GMV were tested. We also quantified the expression levels of KTN1 mRNA in the putamen and/or SNc for comparison between PD and HC in five independent cohorts. Results: Six replicable and two non-replicable KTN1-PD associations were identified (0.009 ≤ p ≤ 0.049). The major alleles of five SNPs, including rs12880292, rs8017172, rs17253792, rs945270, and rs4144657, significantly increased risk for PD (0.020 ≤ p ≤ 0.049) and putamen GMVs (19.08 ≤ β ≤ 60.38; 2.82 ≤ Z ≤ 15.03;

show abstract

Section: Introductionmentioning

confidence: 99%

KTN1 Variants Underlying Putamen Gray Matter Volumes and Parkinson’s Disease

et al. 2020

View full text Add to dashboard Cite

show abstract

“…It is believed that loss of SNC dopamine neurons is detected not only in Parkinson's disease but also in physiological ageing [30,31]. During normal ageing in adult Drosophila melanogaster, Parkin increases lifespan, which is related to an increase in K48 ubiquitin linkage and reduced levels of protein aggregation [32].…”

Section: Discussionmentioning

confidence: 99%

Age-related changes in expression of lysine48 and lysine63 ubiquitin linkages in dopamine neurons of midbrain in mice

Jiang

Liu³

et al. 2021

NeuroReport

View full text Add to dashboard Cite

Ubiquitination of target proteins is mediated via different ubiquitin lysine (K) linkages and determines the protein fates. In particular, K48 ubiquitin linkage targets proteins for degradation, whereas K63 ubiquitin linkage plays a nondegradative role. Parkinson's disease is an age-onset neurodegenerative disorder, which shows selective loss of dopamine neurons in substantia nigra pars compacta (SNC) and ubiquitinated protein aggregates. However, age-related expression of K48 and K63 ubiquitin linkages in SNC dopamine neurons remains elusive. We thus sought to explore the expression of K48 and K63 ubiquitin linkages in dopamine neurons in SNCs of mice at different ages with morphological and biochemical assays. Here our results indicated that in 5-week-old mice, dopamine neurons presented higher levels of K48 and K63 ubiquitin linkages than nondopamine neural cells. Aging promoted the formation of protein aggregates that are positive for both K48 and K63 ubiquitin linkages, together with tyrosine hydroxylase, a dopamine neuron marker. Moreover, 21-month-old mice showed fewer neural cells and tyrosine hydroxylase positive neurons in the SNCs than younger mice. Through biochemical analysis, the 21-month-old mice were shown to express more K48 ubiquitin linkages and less tyrosine hydroxylase and NeuN than the 5-week-old mice. These results suggest the first time that expression of K48 and K63 ubiquitin lysine linkages in midbrain dopamine neurons is age-related and may be involved in the loss of dopamine neurons.

show abstract

Neurochemical and Morphological Changes in the Microstructures of the Compact Part of the Substantia Nigra of the Human Brain in Aging and Parkinson’s Disease (Literature Review)

Cited by 2 publications

References 52 publications

KTN1 Variants Underlying Putamen Gray Matter Volumes and Parkinson’s Disease

KTN1 Variants Underlying Putamen Gray Matter Volumes and Parkinson’s Disease

Age-related changes in expression of lysine48 and lysine63 ubiquitin linkages in dopamine neurons of midbrain in mice

Contact Info

Product

Resources

About