Alpha-Synuclein Aggregation in Parkinson's Disease

Srinivasan, E.; Chandrasekhar, G.; Chandrasekar, P.; Kannan, Anbarasu; Vickram, A.S.; Karunakaran, Rohini; Rajasekaran, R.; Srikumar, P. S.

doi:10.3389/fmed.2021.736978

Cited by 69 publications

(42 citation statements)

References 114 publications

(115 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…α-Synuclein is a key protein in PD physiopathology and point mutations and duplications in its encoding gene, SNCA, are responsible for familial forms of PD (Srinivasan et al, 2021). Four groups have reported that modulating alpha synuclein expression affects ER-mitochondria signaling and its associated functions, such as Ca 2+ homeostasis (Cali et al, 2012;Paillusson et al, 2017), phospholipid synthesis (Guardia-Laguarta et al, 2014), autophagy (Cali et al, 2012), and ATP production (Faustini et al, 2019;Paillusson et al, 2017).…”

Section: Er-mitochondria Signaling In Pdmentioning

confidence: 99%

Endoplasmic reticulum–mitochondria signaling in neurons and neurodegenerative diseases

Markovinović

Greig

Martín‐Guerrero

et al. 2022

Journal of Cell Science

View full text Add to dashboard Cite

Recent advances have revealed common pathological changes in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis with related frontotemporal dementia (ALS/FTD). Many of these changes can be linked to alterations in endoplasmic reticulum (ER)–mitochondria signaling, including dysregulation of Ca2+ signaling, autophagy, lipid metabolism, ATP production, axonal transport, ER stress responses and synaptic dysfunction. ER–mitochondria signaling involves specialized regions of ER, called mitochondria-associated membranes (MAMs). Owing to their role in neurodegenerative processes, MAMs have gained attention as they appear to be associated with all the major neurodegenerative diseases. Furthermore, their specific role within neuronal maintenance is being revealed as mutant genes linked to major neurodegenerative diseases have been associated with damage to these specialized contacts. Several studies have now demonstrated that these specialized contacts regulate neuronal health and synaptic transmission, and that MAMs are damaged in patients with neurodegenerative diseases. This Review will focus on the role of MAMs and ER–mitochondria signaling within neurons and how damage of the ER–mitochondria axis leads to a disruption of vital processes causing eventual neurodegeneration.

show abstract

Section: Er-mitochondria Signaling In Pdmentioning

confidence: 99%

Endoplasmic reticulum–mitochondria signaling in neurons and neurodegenerative diseases

Markovinović

Greig

Martín‐Guerrero

et al. 2022

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…α-syn, encoded by the SCNA gene on chromosome 4, is a highly abundant protein composed of 140 amino acids and widely expressed in the brain (Srinivasan et al, 2021 ). Naturally occurring α-syn consists of three domains: (1) N-terminal lipids bind α-helices, (2) non-amyloid-beta component (NAC) domain, and (3) C-terminal domain rich in acidic residues.…”

Section: α-Syn Pathology In Pdmentioning

confidence: 99%

Hypoxia and Alpha-Synuclein: Inextricable Link Underlying the Pathologic Progression of Parkinson's Disease

Guo

Liu

2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, with typical motor symptoms as the main clinical manifestations. At present, there are about 10 million patients with PD in the world, and its comorbidities and complications are numerous and incurable. Therefore, it is particularly important to explore the pathogenesis of PD and find possible therapeutic targets. Because the etiology of PD is complex, involving genes, environment, and aging, finding common factors is the key to identifying intervention targets. Hypoxia is ubiquitous in the natural environment and disease states, and it is considered to be closely related to the etiology of PD. Despite research showing that hypoxia increases the expression and aggregation of alpha-synuclein (α-syn), the most important pathogenic protein, there is still a lack of systematic studies on the role of hypoxia in α-syn pathology and PD pathogenesis. Considering that hypoxia is inextricably linked with various causes of PD, hypoxia may be a co-participant in many aspects of the PD pathologic process. In this review, we describe the risk factors for PD, and we discuss the possible role of hypoxia in inducing PD pathology by these risk factors. Furthermore, we attribute the pathological changes caused by PD etiology to oxygen uptake disorder and oxygen utilization disorder, thus emphasizing the possibility of hypoxia as a critical link in initiating or promoting α-syn pathology and PD pathogenesis. Our study provides novel insight for exploring the pathogenesis and therapeutic targets of PD.

show abstract

“…Although various cell functions of α-syn remain to be established, the protein is known to be involved in some neurodegenerative disorders [ 7 ]. In fact, α-syn is a major component of Lewy bodies [ 8 , 9 , 10 , 11 ] in Parkinson’s disease (PD), and it is often detected in Alzheimer’s disease [ 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Data about the occurrence of the syns family in tumors mostly investigated γ-syn, which may be aberrantly expressed [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

In Pancreatic Adenocarcinoma Alpha-Synuclein Increases and Marks Peri-Neural Infiltration

Bianchini

Giambelluca

Scavuzzo

et al. 2022

IJMS

View full text Add to dashboard Cite

α-Synuclein (α-syn) is a protein involved in neuronal degeneration. However, the family of synucleins has recently been demonstrated to be involved in the mechanisms of oncogenesis by selectively accelerating cellular processes leading to cancer. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers, with a specifically high neurotropism. The molecular bases of this biological behavior are currently poorly understood. Here, α-synuclein was analyzed concerning the protein expression in PDAC and the potential association with PDAC neurotropism. Tumor (PDAC) and extra-tumor (extra-PDAC) samples from 20 patients affected by PDAC following pancreatic resections were collected at the General Surgery Unit, University of Pisa. All patients were affected by moderately or poorly differentiated PDAC. The amount of α-syn was compared between tumor and extra-tumor specimen (sampled from non-affected neighboring pancreatic areas) by using in situ immuno-staining with peroxidase anti-α-syn immunohistochemistry, α-syn detection by using Western blotting, and electron microscopy by using α-syn-conjugated immuno-gold particles. All the methods consistently indicate that each PDAC sample possesses a higher amount of α-syn compared with extra-PDAC tissue. Moreover, the expression of α-syn was much higher in those PDAC samples from tumors with perineural infiltration compared with tumors without perineural infiltration.

show abstract

Alpha-Synuclein Aggregation in Parkinson's Disease

Cited by 69 publications

References 114 publications

Endoplasmic reticulum–mitochondria signaling in neurons and neurodegenerative diseases

Endoplasmic reticulum–mitochondria signaling in neurons and neurodegenerative diseases

Hypoxia and Alpha-Synuclein: Inextricable Link Underlying the Pathologic Progression of Parkinson's Disease

In Pancreatic Adenocarcinoma Alpha-Synuclein Increases and Marks Peri-Neural Infiltration

Contact Info

Product

Resources

About