<i><scp>SYNJ</scp>1</i> gene associated with neonatal onset of neurodegenerative disorder and intractable seizure

Zaabi, Nuha Al; Menhali, Noora Al; Al‐Jasmi, Fatma

doi:10.1002/mgg3.341

Cited by 18 publications

(12 citation statements)

References 11 publications

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“…In addition, the SYNJ1 gene plays essential roles in the nervous and immune systems. SYNJ1 gene mutations are associated with two rare nervous system diseases: early-onset Parkinson's disease and severe neurodegeneration with refractory seizures and recurrent seizures 47 . Deletion of the SYNJ1 gene can lead to seizures 25 .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression profiling after recurrent febrile seizures in rat and emerging role of miR-148a-3p/SYNJ1 axis

Sun

et al. 2021

Sci Rep

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Febrile seizures (FSs) are common neurological disorders in both infants and children, although the precise underlying mechanism remains to be explored, especially in the expression pattern and function of microRNAs (miRNAs). In this report, we aimed to screen new potential miRNAs and examine the role of miR-148a-3p in hippocampal neurons in FS rats via Synaptojanin-1 (SYNJ1). Thirty rats were randomly divided into the normal and FS model groups, which were investigated by miRNA array. This process identified 31 differentially expressed (20 upregulated and 11 downregulated) miRNAs and potential miRNA target genes. In addition, hippocampal neurons were assigned into five groups for different transfections. Apoptosis was detected by TUNEL and flow cytometry. SYNJ1 was identified as a target gene of miR-148-3p. In vitro experiments revealed that inhibition of miR-148a-3p decreased neuronal cell apoptosis. Moreover, overexpression of miR-148a-3p resulted in activation of PI3K/Akt signaling pathway and the apoptosis of hippocampal neurons. MiR-148a-3p inhibitor could reverse the above events. Taken together, our data demonstrated that the hippocampal miRNA expression profiles of a rat model of FS provide a large database of candidate miRNAs and neuron-related target genes. Furthermore, miR-148a-3p acted as a apoptosis enhcaner via the activation of the SYNJ1/PI3K/Akt signaling pathway, highlighting a potential therapeutic target in the treatment of infants with hyperthermia-induced brain injury.

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Section: Discussionmentioning

confidence: 99%

MicroRNA expression profiling after recurrent febrile seizures in rat and emerging role of miR-148a-3p/SYNJ1 axis

Sun

et al. 2021

Sci Rep

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“…The patients exhibited tremor and bradykinesia with mild cerebral cortical atrophy. At the same time, mutations resulting in complete loss of SYNJ1 function have been identified in patients with early infantile epileptic encephalopathy 53, a severe neurodegenerative disorder characterized by epileptic seizures, severe intellectual disability and spastic quadriplegia (Hardies et al, 2016; Al Zaabi et al, 2018). A homozygous truncating mutation in SYNJ1 identified in a patient with intractable seizures also showed neurofibrillary degeneration and presence of tau protein in substantia nigra region of brain (Dyment et al, 2015).…”

Section: Phosphoinositide Signaling and Diseases Of The Human Nervousmentioning

confidence: 99%

Phosphoinositides: Regulators of Nervous System Function in Health and Disease

Raghu

Joseph

Krishnan

et al. 2019

Front. Mol. Neurosci.

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Phosphoinositides, the seven phosphorylated derivatives of phosphatidylinositol have emerged as regulators of key sub-cellular processes such as membrane transport, cytoskeletal function and plasma membrane signaling in eukaryotic cells. All of these processes are also present in the cells that constitute the nervous system of animals and in this setting too, these are likely to tune key aspects of cell biology in relation to the unique structure and function of neurons. Phosphoinositides metabolism and function are mediated by enzymes and proteins that are conserved in evolution, and analysis of knockouts of these in animal models implicate this signaling system in neural function. Most recently, with the advent of human genome analysis, mutations in genes encoding components of the phosphoinositide signaling pathway have been implicated in human diseases although the cell biological basis of disease phenotypes in many cases remains unclear. In this review we evaluate existing evidence for the involvement of phosphoinositide signaling in human nervous system diseases and discuss ways of enhancing our understanding of the role of this pathway in the human nervous system’s function in health and disease.

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“…Homozygous missense mutation at R258Q of SYJN1 is associated with the early onset of Parkinson disease; patients show tremor and bradykinesia with mild cerebral cortical atrophy [ 76 ]. Whereas, the complete loss of SYJN1 function is associated with early onset of epileptic encephalopathy 53, characterized by the occurrence of epileptic seizures, spastic quadriplegia and severe intellectual disability in patients [ 1 , 46 ]. A homozygous truncating mutation in SYNJ1 found in a patient with intractable seizures, formation of neurofibrillary tangles and occurrence of Tau in substantial nigra of the brain [ 37 ].…”

Section: Clinical Relevance Of Phosphoinositides Signalingmentioning

confidence: 99%

Phosphoinositides signaling modulates microglial actin remodeling and phagocytosis in Alzheimer’s disease

Desale

Chinnathambi

2021

Cell Commun Signal

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Alzheimer’s disease is one of the neurodegenerative diseases, characterized by the accumulation of abnormal protein deposits, which disrupts signal transduction in neurons and other glia cells. The pathological protein in neurodegenerative diseases, Tau and amyloid-β contribute to the disrupted microglial signaling pathways, actin cytoskeleton, and cellular receptor expression. The important secondary messenger lipids i.e., phosphatidylinositols are largely affected by protein deposits of amyloid-β in Alzheimer’s disease. Phosphatidylinositols are the product of different phosphatidylinositol kinases and the state of phosphorylation at D3, D4, and D5 positions of inositol ring. Phosphatidylinositol 3,4,5-triphosphate (PI 3, 4, 5-P3) involves in phagocytic cup formation, cell polarization, whereas Phosphatidylinositol 4,5-bisphosphate (PI 4, 5-P2)-mediates the process of phagosomes formation and further its fusion with early endosome.. The necessary activation of actin-binding proteins such as Rac, WAVE complex, and ARP2/3 complex for the actin polymerization in the process of phagocytosis, migration is regulated and maintained by PI 3, 4, 5-P3 and PI 4, 5-P2. The ratio and types of fatty acid intake can influence the intracellular secondary lipid messengers along with the cellular content of phaphatidylcholine and phosphatidylethanolamine. The Amyloid-β deposits and extracellular Tau seeds disrupt phosphatidylinositides level and actin cytoskeletal network that hamper microglial-signaling pathways in AD. We hypothesize that being a lipid species intracellular levels of phosphatidylinositol would be regulated by dietary fatty acids. Further we are interested to understand phosphoinositide-based signaling cascades in phagocytosis and actin remodeling.

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SYNJ1 gene associated with neonatal onset of neurodegenerative disorder and intractable seizure

Cited by 18 publications

References 11 publications

MicroRNA expression profiling after recurrent febrile seizures in rat and emerging role of miR-148a-3p/SYNJ1 axis

MicroRNA expression profiling after recurrent febrile seizures in rat and emerging role of miR-148a-3p/SYNJ1 axis

Phosphoinositides: Regulators of Nervous System Function in Health and Disease

Phosphoinositides signaling modulates microglial actin remodeling and phagocytosis in Alzheimer’s disease

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