Phenotypic spectrum of patients with
            <i>PLA2G6</i>
            mutation and
            <i>PARK14</i>
            -linked parkinsonism

Yoshino, Hideaki; Tomiyama, Hiroyuki; Tachibana, Naoko; Ogaki, Kotaro; Li, Y.; Funayama, Manabu; Hashimoto, Takao; Takashima, Shota; Hattori, Nobutaka

doi:10.1212/wnl.0b013e3181f73649

Cited by 149 publications

(112 citation statements)

References 7 publications

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“…Homozygosity mapping and mutational analyses over the past 5 years reveals a complicated connection with mutations in the PLA2G6 gene at the PARK14 locus. Initially recognized in adult-onset parkinsonism ( 316 ), PLA2G6 gene mutations are now linked to levodopa-responsive parkinsonism with severe impairments in swallowing, dystonia, and pyramidal weakness ( 317,318 ), and to autosomal early-onset parkinsonism ( 313,(318)(319)(320)(321)(322). However, studies among Asian populations are confl icting, where a link between PLA2G6 mutations and Parkinson's disease was reported in Singapore ( 323 ), but not in China ( 324,325 ) or Japan ( 326 ).…”

Section: Ipla 2 ␤ and Diseasesmentioning

confidence: 99%

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

Ramanadham

Ali

Ashley

et al. 2015

Journal of Lipid Research

169

190

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The Ca 2+ -independent phospholipases A 2 (iPLA 2 s) are part of a diverse family of PLA 2 s that hydrolyze the sn -2 substituent from membrane phospholipids to release a free fatty acid and a lysolipid ( 1, 2 ). These enzymes are ubiquitously expressed, and in contrast to secretory PLA 2 s (sPLA 2 s) and cytosolic PLA 2 s (cPLA 2 s), do not require Ca 2+ for either translocation or activity. Some of the fi rst descriptions of iPLA 2 activity were in the mid-to late-1980s with the identifi cation of a plasmalogen-selective PLA 2 in Abstract Among the family of phospholipases A 2 (PLA 2 s) are the Ca 2+ -independent PLA 2 s (iPLA 2 s) and they are designated group VI iPLA 2 s. In relation to secretory and cytosolic PLA 2 s, the iPLA 2 s are more recently described and details of their expression and roles in biological functions are rapidly emerging. The iPLA 2 s or patatin-like phospholipases (PNPLAs) are intracellular enzymes that do not require Ca 2+ for activity, and contain lipase (GXSXG) and nucleotide-binding (GXGXXG) consensus sequences. Though nine PNPLAs have been recognized, PNPLA8 (membraneassociated iPLA 2 ␥ ) and PNPLA9 (cytosol-associated iPLA 2 ␤ ) are the most widely studied and understood. The iPLA 2 s manifest a variety of activities in addition to phospholipase, are ubiquitously expressed, and participate in a multitude of biological processes, including fat catabolism, cell differentiation, maintenance of mitochondrial integrity, phospholipid remodeling, cell proliferation, signal transduction, and cell death. As might be expected, increased or decreased expression of iPLA 2 s can have profound effects on the metabolic state, CNS function, cardiovascular performance, and cell survival; therefore, dysregulation of iPLA 2 s can be a critical factor in the development of many diseases. This review is aimed at providing a general framework of the current understanding of the iPLA 2 s and discussion of the potential mechanisms of action of the iPLA 2 s and related involved lipid mediators. -Ramanadham, S

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Section: Ipla 2 ␤ and Diseasesmentioning

confidence: 99%

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

Ramanadham

Ali

Ashley

et al. 2015

Journal of Lipid Research

169

190

View full text Add to dashboard Cite

show abstract

“…The phenotypes were associated with cognitive and psychiatric problems and dystonic features, pyramidal syndrome [65]. In an Asian group with early onset recessive parkinsonism caused by compound heterozygous mutations in PLA2G6, the phenotype reported were frontotemporal lobar atrophy and dementia [66]. The PLA2G6 gene encodes a protein of phospholipase A2 group VI (PLA2G6), which act as catalysis of fatty acids elimination from phospholipids and involved in maintaining membrane phospholipids homeostasis [67].…”

Section: Pla2g6mentioning

confidence: 99%

Parkinson’s Disease: Insights from Drosophila Model

Ayajuddin¹,

Das²,

Phom³

et al. 2018

Drosophila Melanogaster - Model for Recent Advances in Genetics and Therapeutics

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Parkinson's disease (PD) is a medical condition that has been known since ancient times. It is the second most common neurodegenerative disorder affecting approximately 1% of the population over 50 years. It is characterized by both motor and non-motor symptoms. Most of PD cases are sporadic while 5-10% cases are familial. Environment factors such as exposure to pesticides, herbicides and other heavy metals are expected to be the main cause of sporadic form of the disease. Mutation of the susceptible genes such as SNCA, PINK1, PARKIN, DJ1, and others are considered to be the main cause of the familial form of disease. Drosophila offers many advantages for studying human neurodegenerative diseases and their underlying molecular and cellular pathology. Shorter life span; large number of progeny; conserved molecular mechanism(s) among fly, mice and human; availability of many techniques, and tools to manipulate gene expression makes drosophila a potential model system to understand the pathology associated with PD and to unravel underlying molecular mechanism(s) responsible for dopaminergic neurodegeneration in PD-understanding of which will be of potential assistance to develop therapeutic strategies to PD. In the present review, we made an effort to discuss the contribution of fly model to understand pathophysiology of PD, in understanding the biological functions of genes implicated in PD; to understand the gene-environment interaction in PD; and validation of clues that are generated through genome-wide association studies (GWAS) in human through fly; further to screen and develop potential therapeutic molecules for PD. In nutshell, fly has been a great model system which has immensely contributed to the biomedical research relating to understand and addressing the pathology of human neurological diseases in general and PD in particular.

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“…These mutations were also associated with neurodegeneration with iron accumulation in brain and to Karak syndrome, both severe forms of childlike neurodegeneration [129,130]. PD associated with this gene has recessive transmission or dominant when there are several missense mutations [131,132].…”

Section: +mentioning

confidence: 99%

Genes involved in the development of Parkinson

Teixeira¹,

Cardoso²

2017

Open J Parkinsons Dis Treatm

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Background: Parkinson's disease is the second most important neurodegenerative disorder, affecting 3% of individuals older than 80 years of age. Main clinical symptoms are resting tremor, postural instability, bradykinesia and rigidity, with a good response to levodopa therapy. Purpose of the study:The main goal of this work is to make a deep analysis on the genetic factors and kind of heritage involved in the development of Parkinson. Main fi ndings:Over the last years, numerous studies allowed to confirm the unquestionable contribution of genetic factors to the complex pathogenesis of this disease. Highly penetrant mutations producing rare, monogenic forms of the disease have been identifi ed in singular genes such as SNCA, Parkin, DJ-1, PINK1, LRRK2, and VPS35. Unique variants with incomplete penetrance in LRRK2 and GBA genes were identifi ed as strong risk factors for Parkinson's disease in certain populations. Additionally, over 20 common variants with small effect sizes are now recognized to modulate the risk for Parkinson's disease.Investigating Mendelian forms of Parkinson disease has provided precious insight into the pathophysiology that underlies the more common idiopathic form of this disorder. Conclusions:The challenge over the next decade will be to get more data that strengthens the already available knowledge concerning genetics on Parkinson's disease, through the discovery of biological consequences of risk variants. Moreover, it is also expected that the advent of genome-wide association studies and the implementation of new research technologies will help in the identifi cation of novel risk variants for the sporadic forms of Parkinson disease.

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Phenotypic spectrum of patients with PLA2G6 mutation and PARK14 -linked parkinsonism

Cited by 149 publications

References 7 publications

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

Parkinson’s Disease: Insights from Drosophila Model

Genes involved in the development of Parkinson

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