Genetic variants and animal models in SNCA and Parkinson disease

Deng, Hao; Yuan, Lamei

doi:10.1016/j.arr.2014.04.002

Cited by 82 publications

(62 citation statements)

References 235 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mutations (A53T, A30P, and E46K) or duplication or triplication of WT α-synuclein have been associated with rare forms of familial PD (9)(10)(11)(12). Many α-synuclein transgenic mouse models of the familial forms of PD due to mutations in α-synuclein have been created (7,(13)(14)(15)(16)(17). These models replicate many of the features of α-synucleinopathy-induced neurodegeneration that is present in human PD and diffuse Lewy body disease (7,(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

“…Many α-synuclein transgenic mouse models of the familial forms of PD due to mutations in α-synuclein have been created (7,(13)(14)(15)(16)(17). These models replicate many of the features of α-synucleinopathy-induced neurodegeneration that is present in human PD and diffuse Lewy body disease (7,(13)(14)(15)(16)(17). Posttranslational modifications of α-synuclein such as nitrosylation, oxidation, and phosphorylation play a role in modulating α-synuclein aggregation and toxicity (18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Activation of tyrosine kinase c-Abl contributes to α-synuclein–induced neurodegeneration

Brahmachari¹,

Lee

et al. 2016

Journal of Clinical Investigation

146

184

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activation of tyrosine kinase c-Abl contributes to α-synuclein–induced neurodegeneration

Brahmachari¹,

Lee

et al. 2016

Journal of Clinical Investigation

146

184

View full text Add to dashboard Cite

“…By 30 years of age, the α-syn-positive neurons reach five times more than those at 10 years of age, and, finally, most of the remaining nigral dopamine neurons express α-syn. It is known that familial PD, i.e., PARK1 and PARK4, is characterized by rapid α-syn accumulation and early disease onset [32]. On the other hand, the disease onset is usually seen late (at older ages) in most cases of sporadic PD in which as many as 60-80% of nigral dopamine neurons are damaged when motor symptoms occur [33][34][35][36].…”

Section: Discussionmentioning

confidence: 99%

Propagated but topologically distributed forebrain neurons expressing alpha-synuclein in aged macaques

Kimura

Inoue

Kuroiwa

et al. 2017

Journal of the Neurological Sciences

View full text Add to dashboard Cite

In neurodegenerative disorders, such as Parkinson's disease (PD), alpha-synuclein (α-syn) accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB). This α-syn-related pathology is termed synucleinopathy. It remains unclear how α-syn accumulation expands during the progress of synucleinopathy in the human brain. In our study, we investigated the patterns of distribution and propagation of forebrain neurons expressing α-syn in aged macaques. It was found that the occurrence of α-syn-positive neurons proceeded topologically based on the midbrain dopamine pathways arising from the substantia nigra and the ventral tegmental area where they were primarily observed. In the nigrostriatal or mesolimbic dopamine pathway, the age-dependent increase in α-syn-positive neurons was evident in the striatum or the nucleus accumbens, respectively. Concerning the nigrostriatal pathway, a mediolateral or rostrocaudal gradient was seen in the substantia nigra or the striatum, respectively, and a compensatory increase in dopamine transporter occurred in the striatum regardless of the decreased dopamine level. In the mesocortical dopamine pathway, α-syn-positive neurons appeared in the prefrontal and then motor areas of the frontal lobe. Given that neither LB formation nor clinical phenotype manifestation was detected in any of the monkeys examined in the present study, aged macaques may be useful as a potential presymptomatic model for PD and LB-related neuropsychiatric disorders.

show abstract

“…Over 20 loci and 15 disease-causing genes for Parkinsonism have been identifi ed [150]. Mutations in seven genes are robustly associated with autosomal dominant (SNCA, LRRK2, EIF4G1, VPS35) or recessive (parkin/ PARK2, PINK1, DJ1/ PARK7) PD.…”

Section: Genetics In Pdmentioning

confidence: 99%

Restoration of Mitochondrial Dysfunction in 6-Hydroxydopamine Induced Parkinson’s disease: a Complete Review

Mehan¹,

Kaur²,

Dudi³

et al. 2017

Open J Parkinsons Dis Treatm

View full text Add to dashboard Cite

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by neuronal cell death in the specifi c brain region like basal ganglia, cerebral cortex and hippocampus. Symptoms associated with PD patients are rigidity, akathesia, tremor, postural imbalance, cognitive and memory dysfunctions. Pathological hallmarks are dopaminergic neuronal degeneration, neuro-infl ammation, oxidative stress, free radical generation. In the typical Parkinson's disease model, 6-Hydroxydopamine (6-OHDA) is delivered unilaterally by stereotactic injection into the SNc (substantia nigra pars-compacta) or the striatum mimics the PD symptoms. In addition, it has been shown that 6-OHDA is toxic to complex I & IV of the mitochondrial respiratory chain, leading to subsequent respiratory inhibition and further processed ATP depletion, oxidative stress and neuro-infl ammation. Forskolin (FSK), a diterpene natural plant phytochemical obtained from (Coleus Forskohli), a potent direct activator of adenyl cyclase (AC) enzyme which further activates cAMP/PK A /CREB pathway. FSK mediated activation of AC/cAMP/PK A / CREB pathway is responsible for various neuroprotective mechanisms Based on important and versatile role of FSK, the present study has been designed to investigate the role of cAMP mediated CREB activation in 6-hydroxydopamine induced mitochondrial associated neurotoxicity in rats. Further the studies are extended to understand the disease pathogenesis and to investigate and discuss the various possible central mechanisms involved in the effect of such targets using behavioral paradigm and biochemical markers of neurodegeneration.

show abstract

Genetic variants and animal models in SNCA and Parkinson disease

Cited by 82 publications

References 235 publications

Activation of tyrosine kinase c-Abl contributes to α-synuclein–induced neurodegeneration

Activation of tyrosine kinase c-Abl contributes to α-synuclein–induced neurodegeneration

Propagated but topologically distributed forebrain neurons expressing alpha-synuclein in aged macaques

Restoration of Mitochondrial Dysfunction in 6-Hydroxydopamine Induced Parkinson’s disease: a Complete Review

Contact Info

Product

Resources

About