Pax6 Binds to Promoter Sequence Elements Associated with Immunological Surveillance and Energy Homeostasis in Brain of Aging Mice

Maurya, Shashank Kumar; Mishra, Rajnikant

doi:10.1159/000464419

Cited by 20 publications

(10 citation statements)

References 21 publications

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“…In an elegant study, Maurya & Mishra (2017) demonstrated age-dependent alterations in PAX6 binding to the regulatory elements of genes involved in immunological surveillance and energy homeostasis [93]. Also, they evidenced an interaction of PAX6 with the Presenilin-1 regulatory element, which indicates its role in AD pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Maekawa et al (2006) utilized a PAX6-deficient rat model to elucidate the essential role of PAX6 in the production and maintenance of early NPC in the postnatal hippocampal neurogenesis [92]. Moreover, patients with PAX6 mutations demonstrate phenotypes that match age-associated neurological disorders [93]. Animal models prove the progressive age-associated reduction in the PAX6 brain levels [94].…”

Section: Discussionmentioning

confidence: 99%

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Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer’s Disease Mice

Polis

Srikanth

Gurevich

et al. 2020

IJMS

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Adult neurogenesis is a complex physiological process, which plays a central role in maintaining cognitive functions, and consists of progenitor cell proliferation, newborn cell migration, and cell maturation. Adult neurogenesis is susceptible to alterations under various physiological and pathological conditions. A substantial decay of neurogenesis has been documented in Alzheimer’s disease (AD) patients and animal AD models; however, several treatment strategies can halt any further decline and even induce neurogenesis. Our previous results indicated a potential effect of arginase inhibition, with norvaline, on various aspects of neurogenesis in triple-transgenic mice. To better evaluate this effect, we chronically administered an arginase inhibitor, norvaline, to triple-transgenic and wild-type mice, and applied an advanced immunohistochemistry approach with several biomarkers and bright-field microscopy. Remarkably, we evidenced a significant reduction in the density of neuronal progenitors, which demonstrate a different phenotype in the hippocampi of triple-transgenic mice as compared to wild-type animals. However, norvaline showed no significant effect upon the progenitor cell number and constitution. We demonstrated that norvaline treatment leads to an escalation of the polysialylated neuronal cell adhesion molecule immunopositivity, which suggests an improvement in the newborn neuron survival rate. Additionally, we identified a significant increase in the hippocampal microtubule-associated protein 2 stain intensity. We also explore the molecular mechanisms underlying the effects of norvaline on adult mice neurogenesis and provide insights into their machinery.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer’s Disease Mice

Polis

Srikanth

Gurevich

et al. 2020

IJMS

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“…Quantitative RT-PCR was performed using ThunderBird® STBR® qPCR mix (TOYOBO). The primers used for q RT-PCR were as follows: SOD forward 5’-TGGGGACAATACACAAGGCTGT-3’ and reverse 5’-TTTCCACCTTTGCCCAAGTCA-3’; Catalase forward 5’-CCTCCTCGTTCAGGATGTGGTT-3’ and reverse 5’-CGAGGGTCACGAACTGTGTCAG-3’; GPx forward 5’-CCGGGACTACACCGAGATGAA-3’ and reverse 5’-CACCAGGTCGGACGTACTTGAG-3’; GAPDH, forward 5′-CGACTTCAA-CAGCAACTCCCACTCTTCC-3′ and reverse 5′-TGGGTGG-TCCAGGGTTTCTTACTCCTT-3′ [ 31 , 32 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

“…GPx forward 5'-CCGGGACTACACCGAGATGAA-3' and reverse 5'-CACCAGGTCGGACGTACTTGAG-3'; GAPDH, forward 5 -CGACTTCAA-CAGCAACTCCCACTCTTCC-3 and reverse 5 -TGGGTGG-TCCAGGGTTTCTTACTCCTT-3 [31][32][33].…”

Section: Real-time Quantitative Pcrmentioning

confidence: 99%

Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer

Kim

Jeena

Kim

et al. 2020

IJMS

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Here, we provide the possibility of a novel chemotherapeutic agent against gastric cancer cells, comprising the combination of 5-fluorouracil (5-FU) and a mitochondria-targeting self-assembly peptide, which is a phenylalanine dipeptide with triphenyl phosphonium (Mito-FF). The anticancer effects and mechanisms of 5-FU and Mito-FF, individually or in combination, were compared through both in vitro and in vivo models of gastric cancer. Our experiments consistently demonstrated that the 5-FU and Mito-FF combination therapy was superior to monotherapy with either, as manifested by both higher reduction of proliferation as well as an induction of apoptotic cell death. Interestingly, we found that combining 5-FU with Mito-FF leads to a significant increase of reactive oxygen species (ROS) and reduction of antioxidant enzymes in gastric cancer cells. Moreover, the inhibition of ROS abrogated the pro-apoptotic effects of combination therapy, suggesting that enhanced oxidative stress could be the principal mechanism of the action of combination therapy. We conclude that the combination of 5-FU and Mito-FF exerts potent antineoplastic activity against gastric cancer cells, primarily by promoting ROS generation and suppressing the activities of antioxidant enzymes.

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“…PAX6 is a highly conserved transcription factor critical to the control of both ocular and neural development (Prosser and van Heyningen 1998). In addition to orchestrating the developing eye, it is expressed in the central nervous system and pancreas, as well as in adult tissues such as the cornea, brain and pancreas where it is involved in homeostasis (Sivak et al 2003; Hart et al 2013; Yogarajah et al 2016; Huettl et al 2016; Maurya and Mishra 2017).…”

Section: Classical Aniridiamentioning

confidence: 99%

The genetic architecture of aniridia and Gillespie syndrome

2018

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Absence of part or all of the iris, aniridia, is a feature of several genetically distinct conditions. This review focuses on iris development and then the clinical features and molecular genetics of these iris malformations. Classical aniridia, a panocular eye malformation including foveal hypoplasia, is the archetypal phenotype associated with heterozygous PAX6 loss-of-function mutations. Since this was identified in 1991, many genetic mechanisms of PAX6 inactivation have been elucidated, the commonest alleles being intragenic mutations causing premature stop codons, followed by those causing C-terminal extensions. Rarely, aniridia cases are associated with FOXC1, PITX2 and/or their regulatory regions. Aniridia can also occur as a component of many severe global eye malformations. Gillespie syndrome—a triad of partial aniridia, non-progressive cerebellar ataxia and intellectual disability—is phenotypically and genotypically distinct from classical aniridia. The causative gene has recently been identified as ITPR1 . The same characteristic Gillespie syndrome-like iris, with aplasia of the pupillary sphincter and a scalloped margin, is seen in ACTA2 -related multisystemic smooth muscle dysfunction syndrome. WAGR syndrome (Wilms tumour, aniridia, genitourinary anomalies and mental retardation/intellectual disability), is caused by contiguous deletion of PAX6 and WT1 on chromosome 11p. Deletions encompassing BDNF have been causally implicated in the obesity and intellectual disability associated with the condition. Lastly, we outline a genetic investigation strategy for aniridia in light of recent developments, suggesting an approach based principally on chromosomal array and gene panel testing. This strategy aims to test all known aniridia loci—including the rarer, life-limiting causes—whilst remaining simple and practical.

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Pax6 Binds to Promoter Sequence Elements Associated with Immunological Surveillance and Energy Homeostasis in Brain of Aging Mice

Cited by 20 publications

References 21 publications

Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer’s Disease Mice

Arginase Inhibition Supports Survival and Differentiation of Neuronal Precursors in Adult Alzheimer’s Disease Mice

Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer

The genetic architecture of aniridia and Gillespie syndrome

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