Cell Responses to Extracellular α-Synuclein

Surguchev, Alexei; Emamzadeh, Fatemeh Nouri; Surguchov, Andrei

doi:10.3390/molecules24020305

Cited by 35 publications

(33 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This cooperation fosters the transmission of α-syn between cells and causes synaptic dysfunction via a signaling cascade acting through phosphorylation of Fyn kinase and activation of the N-methyl-D-aspartate receptor (NMDAR). α-syn-PrP C binding induces cofilin/actin rods formation, which changes actin dynamics, resulting in rearrangements of cytoskeleton and eventual synaptic dysfunction (Clavaguera et al, 2015; Bras et al, 2018; Surguchev et al, 2019). Equally, α-syn amyloids blocked the replication of PrP Sc in vitro and ex vivo (Aulic et al, 2017).…”

Section: The Prion-like Mechanism Of Pdmentioning

confidence: 99%

Prion-Like Mechanisms in Parkinson’s Disease

et al. 2019

View full text Add to dashboard Cite

Formation and aggregation of misfolded proteins in the central nervous system (CNS) is a key hallmark of several age-related neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). These diseases share key biophysical and biochemical characteristics with prion diseases. It is believed that PD is characterized by abnormal protein aggregation, mainly that of α-synuclein (α-syn). Of particular importance, there is growing evidence indicating that abnormal α-syn can spread to neighboring brain regions and cause aggregation of endogenous α-syn in these regions as seeds, in a “prion-like” manner. Abundant studies in vitro and in vivo have shown that α-syn goes through a templated conformational change, propagates from the original region to neighboring regions, and eventually cause neuron degeneration in the substantia nigra and striatum. The objective of this review is to summarize the mechanisms involved in the aggregation of abnormal intracellular α-syn and its subsequent cell-to-cell transmission. According to these findings, we look forward to effective therapeutic perspectives that can block the progression of neurodegenerative diseases.

show abstract

Section: The Prion-like Mechanism Of Pdmentioning

confidence: 99%

Prion-Like Mechanisms in Parkinson’s Disease

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In addition, Surguchev et al showed that extracellular α-synuclein interacts with cell membrane receptors such as cytoplasmic protein, lymphocyte activating gene 3, and Toll-like receptor 2. Cell signaling promotes α-synuclein to propagate between different cells [123]. The above results together indicate that in the neurons of patients with familial Parkinson's disease caused by genetic mutations, their α-synuclein pathology has sufficient seed characteristics to cause agedependent human neuronal degeneration spread in brains.…”

Section: Ipsc Models Confirm the Neuron-to-neuronmentioning

confidence: 82%

Modeling Parkinson’s Disease Using Induced Pluripotent Stem Cells

Mao

Fan

et al. 2020

Stem Cells International

View full text Add to dashboard Cite

Parkinson’s disease (PD) is the second most common neurodegenerative disease. The molecular mechanisms of PD at the cellular level involve oxidative stress, mitochondrial dysfunction, autophagy, axonal transport, and neuroinflammation. Induced pluripotent stem cells (iPSCs) with patient-specific genetic background are capable of directed differentiation into dopaminergic neurons. Cell models based on iPSCs are powerful tools for studying the molecular mechanisms of PD. The iPSCs used for PD studies were mainly from patients carrying mutations in synuclein alpha (SNCA), leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), parkin RBR E3 ubiquitin protein ligase (PARK2), cytoplasmic protein sorting 35 (VPS35), and variants in glucosidase beta acid (GBA). In this review, we summarized the advances in molecular mechanisms of Parkinson’s disease using iPSC models.

show abstract

“…Several proteins such as PrPC, LAG3, neurexin1, TLR2 and mGluR5 that function as receptors for the extracellular α-synuclein have been identified [ 129 , 130 ]. The pathological effects caused due to binding of α-synuclein to cell surface receptors is under investigation and is proposed to occur by various mechanisms (for a recent review, see [ 131 ]). Ca 2+ dysregulation, synaptic dysfunction, altered glutamatergic synaptic transmission and α3-Na + /K + -ATPase activity as a result of extracellular α-synuclein have been reported [ 132 , 133 ].…”

Section: α-Synuclein: Folding Higher-order Structures and Degradamentioning

confidence: 99%

Chaperones and Proteostasis: Role in Parkinson’s Disease

2020

View full text Add to dashboard Cite

Proper folding to attain a defined three-dimensional structure is a prerequisite for the functionality of a protein. Improper folding that eventually leads to formation of protein aggregates is a hallmark of several neurodegenerative disorders. Loss of protein homeostasis triggered by cellular stress conditions is a major contributing factor for the formation of these toxic aggregates. A conserved class of proteins called chaperones and co-chaperones is implicated in maintaining the cellular protein homeostasis. Expanding the body of evidence highlights the role of chaperones as central mediators in the formation, de-aggregation and degradation of the aggregates. Altered expression and function of chaperones is associated with many neurodegenerative diseases including Parkinson’s disease. Several studies indicate that chaperones are at the center of the cause and effect cycle of this disease. An overview of the various chaperones that are associated with homeostasis of Parkinson’s disease-related proteins and their role in pathogenicity will be discussed in this review.

show abstract

Cell Responses to Extracellular α-Synuclein

Cited by 35 publications

References 42 publications

Prion-Like Mechanisms in Parkinson’s Disease

Prion-Like Mechanisms in Parkinson’s Disease

Modeling Parkinson’s Disease Using Induced Pluripotent Stem Cells

Chaperones and Proteostasis: Role in Parkinson’s Disease

Contact Info

Product

Resources

About