Редактирование: SPN (раздел)

==Publications==

{{medline-entry
|title=Parkinson's disease-related Leucine-rich repeat kinase 2 modulates nuclear morphology and genomic stability in striatal projection neurons during aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32075681
|abstract=Multiple missense mutations in Leucine-rich repeat kinase 2 ([[LRRK2]]) are associated with familial forms of late onset Parkinson's disease (PD), the most common age-related movement disorder. The dysfunction of dopamine transmission contributes to PD-related motor symptoms. Interestingly, [[LRRK2]] is more abundant in the dopaminoceptive striatal spiny projection neurons ([[SPN]]s) compared to the dopamine-producing nigrostriatal dopaminergic neurons. Aging is the most important risk factor for PD and other neurodegenerative diseases. However, whether [[LRRK2]] modulates the aging of [[SPN]]s remains to be determined. We conducted RNA-sequencing (RNA-seq) analyses of striatal tissues isolated from Lrrk2 knockout (Lrrk2 ) and control (Lrrk2 ) mice at 2 and 12 months of age. We examined [[SPN]] nuclear DNA damage and epigenetic modifications; [[SPN]] nuclear, cell body and dendritic morphology; and the locomotion and motor skill learning of Lrrk2  and Lrrk2  mice from 2 to 24 months of age. Considering the strength of cell cultures for future mechanistic studies, we also performed preliminary studies in primary cultured [[SPN]]s derived from the Lrrk2  and Lrrk2  mice as well as the PD-related Lrrk2 G2019S and R1441C mutant mice. Lrrk2-deficiency accelerated nuclear hypertrophy and induced dendritic atrophy, soma hypertrophy and nuclear invagination in [[SPN]]s during aging. Additionally, increased nuclear DNA damage and abnormal histone methylations were also observed in aged Lrrk2  striatal neurons, together with alterations of molecular pathways involved in regulating neuronal excitability, genome stability and protein homeostasis. Furthermore, both the PD-related Lrrk2 G2019S mutant and [[LRRK2]] kinase inhibitors caused nuclear hypertrophy, while the Lrrk2 R1441C mutant and γ-Aminobutyric acid type A receptor (GABA-AR) inhibitors promoted nuclear invagination in the cultured [[SPN]]s. On the other hand, inhibition of neuron excitability prevented the formation of nuclear invagination in the cultured Lrrk2  and R1441C [[SPN]]s. Our findings support an important physiological function of [[LRRK2]] in maintaining nuclear structure integrity and genomic stability during the normal aging process, suggesting that PD-related [[LRRK2]] mutations may cause the deterioration of neuronal structures through accelerating the aging process.

|keywords=* And aging
* Dendritic hypotrophy
* Excitability
* G2019S
* GABAA
* LRRK2
* Nuclear DNA damage
* Nuclear hypertrophy
* Nuclear invagination
* Parkinson’s disease
* R1441C
* Striatal spiny projection neuron
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031993
}}
{{medline-entry
|title=[Identification of single nucleotide polymorphisms in centenarians].
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26541311
|abstract=Longevity is determined by genetic and external factors, such as nutritional, environmental, social, etc. Nevertheless, when living conditions are optimal, longevity is determined by genetic variations between individuals. In a same population, with relative genotypic homogeneity, subtle changes in the DNA sequence affecting a single nucleotide can be observed. These changes, called single nucleotide polymorphisms (SNP) are present in 1-5% of the population. A total of 92 subjects were recruited, including 28 centenarians and 64 controls, in order to find SNP that maybe implicated in the extreme longevity, as in the centenarians. Blood samples were collected to isolate and amplify the DNA in order to perform the analysis of [[SPN]] by Axiom™ Genotyping of Affymetrix technology. Statistical analyses were performed using the Plink program and libraries SNPassoc and skatMeta. Our results show 12 mutations with a p<.001, where 5 of these (DACH1, LOC91948, BTB16, [[NFIL3]] y HDAC4) have regulatory functions of the expressions of others genes. Therefore, these results suggest that the genetic variation between centenarians and controls occurs in five genes that are involved in the regulation of gene expression to adapt to environmental changes better than controls.
|mesh-terms=* Adaptation, Physiological
* Aged, 80 and over
* Female
* Gene Expression
* Genotype
* Humans
* Longevity
* Male
* Polymorphism, Single Nucleotide
|keywords=* Ageing
* Centenarian
* Centenarios
* Envejecimiento
* Extreme longevity
* Longevidad
* Longevidad extrema
* Longevity
|full-text-url=https://sci-hub.do/10.1016/j.regg.2015.09.006
}}