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Keeping α-Synuclein at Bay: A More Active Role of Molecular Chaperones in Preventing Mitochondrial Interactions and Transition to Pathological States?

Emelie E. Aspholm, Irena Matečko-Burmann, Björn M. Burmann
2020 Life  
as well as the possible proteolytic processing of α-synuclein by mitochondrial proteases.  ...  Here, we will review the current knowledge on the role of molecular chaperones in the regulation of physiological functions as well as the direct consequences of impairing these interactions—i.e., leading  ...  Conflicts of Interest: The authors declare no competing interest.  ... 
doi:10.3390/life10110289 pmid:33227899 fatcat:ry3sfunn5rehjgzeztysu75xba

Molecular Chaperones and Co-Chaperones in Parkinson Disease

Hemi Dimant, Darius Ebrahimi-Fakhari, Pamela J. McLean
2012 The Neuroscientist  
Parkinson disease, a progressive neurodegenerative disorder, is caused by the pathological accumulation of proteins, including the ubiquitous presynaptic protein α-synuclein.  ...  Important to Parkinson disease, chaperones are capable of preventing α-synuclein misfolding, oligomerization, and aggregate formation as shown in vitro and in Parkinson disease animal models.  ...  Acknowledgments Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institutes  ... 
doi:10.1177/1073858412441372 pmid:22829394 pmcid:PMC3904222 fatcat:leetaykrcnaelkn76bcpfgt4su

Chaperones and Proteostasis: Role in Parkinson's Disease

Neha Joshi, Atchaya Raveendran, Shirisha Nagotu
2020 Diseases  
A conserved class of proteins called chaperones and co-chaperones is implicated in maintaining the cellular protein homeostasis.  ...  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.  ...  Conflicts of Interest: The authors declare no conflict of interest.  ... 
doi:10.3390/diseases8020024 pmid:32580484 fatcat:6anrcvsarzf65kgglpf5zfnmti

Ambroxol hydrochloride, a chaperone therapy for Paget's disease of bone and other common autophagy-mediated aging diseases?

Mohamed Numan
2017 Integrative Clinical Medicine  
Furthermore, some familial forms of Parkinson's disease caused by point mutations and multiplications of the whole locus at α-synuclein gene [21] . α-synuclein overexpression suppresses macroautophagy  ...  Moreover, it suppresses α-synuclein overexpression neuroblastoma cell lines [2] .  ... 
doi:10.15761/icm.1000107 fatcat:ja65qiyblbfnrnwe4rf4xq77qu

Alpha-synuclein, Proteotoxicity and Parkinson's Disease: Search for Neuroprotective Therapy

Upasana Ganguly, Sankha Shubhra Chakrabarti, Upinder Kaur, Anwesha Mukherjee, Sasanka Chakrabarti
2018 Current Neuropharmacology  
This important role of α-synuclein in PD pathogenesis is supported by the fact that duplication, triplication and mutations of α-synuclein gene cause familial forms of PD.  ...  There is a growing body of evidence in animal and cell based models of Parkinson's disease (PD) to suggest that overexpression and / or abnormal accumulation and aggregation of α-synuclein can trigger  ...  SSC and UK thank the National Programme for Healthcare of the Elderly, Ministry of Health and Family Welfare, Govt. of India for support in their research work.  ... 
doi:10.2174/1570159x15666171129100944 pmid:29189163 pmcid:PMC6120113 fatcat:3jb23p6rcrhblgd6aezfaev6ya

Cellular proteostasis: degradation of misfolded proteins by lysosomes

M. P. Jackson, E. W. Hewitt
2016 Essays in Biochemistry  
Conversely, amyloid diseases represent a failure in proteostasis, in which proteins misfold, forming amyloid deposits that are not degraded effectively by cells.  ...  However, targeting the pathways that regulate autophagy and the biogenesis of lysosomes may present approaches that can rescue cells from the deleterious effects of amyloidogenic proteins.  ...  The mTOR (mammalian target of rapamycin) complex regulates macroautophagy [10] .  ... 
doi:10.1042/ebc20160005 pmid:27744333 pmcid:PMC5065703 fatcat:ounjkawcnfgxrcmewiqmosse4i

Ferritinophagy and α-Synuclein: Pharmacological Targeting of Autophagy to Restore Iron Regulation in Parkinson's Disease

Matthew K. Boag, Angus Roberts, Vladimir N. Uversky, Linlin Ma, Des R. Richardson, Dean L. Pountney
2022 International Journal of Molecular Sciences  
This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of α-synuclein protein aggregates.  ...  The scope of this review is to describe the physiological and pathological relationship between iron regulation and α-synuclein, providing a detailed understanding of iron metabolism within nigral neurons  ...  Further studies are required to determine if this IRE plays any role in the regulation of α-synuclein expression by iron.  ... 
doi:10.3390/ijms23042378 pmid:35216492 pmcid:PMC8878351 fatcat:bjjovshhm5b2hk365tgto4f55i

Balancing mTOR Signaling and Autophagy in the Treatment of Parkinson's Disease

Zhou Zhu, Chuanbin Yang, Ashok Iyaswamy, Senthilkumar Krishnamoorthi, Sravan Gopalkrishnashetty Sreenivasmurthy, Jia Liu, Ziying Wang, Benjamin Chun-Kit Tong, Juxian Song, Jiahong Lu, King-Ho Cheung, Min Li
2019 International Journal of Molecular Sciences  
The mammalian target of rapamycin (mTOR) signaling pathway plays a critical role in regulating cell growth, proliferation, and life span. mTOR signaling is a central regulator of autophagy by modulating  ...  Parkinson's disease (PD) is a serious, common neurodegenerative disease characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc) and the accumulation of Lewy bodies.  ...  For example, curcumin, culinary spice, plays a neuroprotective role in an A53T α-synuclein cell model of PD by enhancing autophagic degradation of A53T α-synuclein via inhibiting mTOR/P70S6K signaling  ... 
doi:10.3390/ijms20030728 fatcat:cxwlbvq66ndwrmxwzq6jtcrgn4

Role of the unfolded protein response in the pathogenesis of Parkinson's disease

Deeksha Varma, Dwaipayan Sen
2015 Acta Neurobiologiae Experimentalis  
It is is characterized by loss of dopaminergic neurons in the striatum and substantia nigra, coupled with the formation of intracellular Lewy bodies in degenerating neurons.  ...  Recent evidence suggests endoplasmic reticulum stress as a common and prominent occurrence in the progression of Parkinson's disease pathogenesis in the affected human brain.  ...  intermembrane space (IMS) of MT in mammalian cells.  ... 
pmid:25856519 fatcat:sv5fyapqgffvdhdohc22csn2em

Lysosomal impairment in Parkinson's disease

Benjamin Dehay, Marta Martinez-Vicente, Guy A. Caldwell, Kim A. Caldwell, Zhenyue Yue, Mark R. Cookson, Christine Klein, Miquel Vila, Erwan Bezard
2013 Movement Disorders  
In addition, PD-linked mutations and post-translational modifications of α-synuclein impair its own lysosomal-mediated degradation, thereby contributing to its accumulation and aggregation.  ...  New data offer mechanistic molecular evidence for such a connection, unraveling a causal link between lysosomal impairment, α-synuclein accumulation,  ...  and co-chaperones, determine the degradation destiny of α-synuclein.  ... 
doi:10.1002/mds.25462 pmid:23580333 pmcid:PMC5131721 fatcat:n47pl6u4pndrvhrp5qybe5suw4

Identification of common genetic modifiers of neurodegenerative diseases from an integrative analysis of diverse genetic screens in model organisms

Xi Chen, Robert D Burgoyne
2012 BMC Genomics  
Of the common genetic regulators some such as chaperones, ubiquitin-related enzymes (including the E3 ligase CHIP which directly links the two pathways) and histone deacetylases were involved in expected  ...  Combination of data from 28 published studies using small to large scale screens in all three small model organisms gave a total of 950 identifications of genetic regulators.  ...  Acknowledgements This work was supported by a BBSRC Studentship to XC.  ... 
doi:10.1186/1471-2164-13-71 pmid:22333271 pmcid:PMC3292922 fatcat:wmivxizzdndmxd656jk5ah5hby

The impact of genetic research on our understanding of Parkinson's disease [chapter]

Ian Martin, Valina L. Dawson, Ted M. Dawson
2010 Progress in Brain Research  
of this chapter. transgenic mice expressing both α-synuclein and amyloid-β neuronally developed more αsynuclein-immunoreactive inclusions than singly α-synuclein transgenic mice.  ...  Until recently, genetics was thought to play a minor role in the development of Parkinson's disease (PD).  ...  Acknowledgements This work was supported by grants from NIH/NINDS P50 NS38377, NS054207. T.M.D. is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases.  ... 
doi:10.1016/s0079-6123(10)83002-x pmid:20696313 pmcid:PMC4451604 fatcat:bzvrh5tsxfbjbccfks6mdcjfl4


Nancy M. Bonini, Mark E. Fortini
2003 Annual Review of Neuroscience  
The findings highlight Drosophila as an important model system in which to study the fundamental pathways influenced by these genes and have led to new insights into aspects of pathogenesis and modifier  ...  disease s Abstract A number of approaches have been taken to recreate and to study the role of genes associated with human neurodegenerative diseases in the model organism Drosophila.  ...  Drugs that upregulate chaperones lessen polyglutamine toxicity in mammalian cell models (Sittler et al. 2001 ) and also function in vivo to reduce α-synuclein toxicity in Parkinson's disease models (  ... 
doi:10.1146/annurev.neuro.26.041002.131425 pmid:12704223 fatcat:5rwyj5kn2ncm7okw6quhh2c63y

Patterns of synuclein expression throughout lens development

Irina Surgucheva, Belinda MacMahon, Andrei Surguchov
2010 Journal of Biophysical Chemistry  
Synucleins belong to a family of small soluble proteins with chaperonic activity implicated in human diseases, but their normal function is not completely understood.  ...  These results suggest that -synuclein plays a role in distinct temporal events in lens development, presumably acting as a specific chaperone.  ...  Interestingly, the study of synuclein expression in the mammalian cochlea showed that developmentally, -synuclein can be seen in the region of the outer hair cells by E19, whereas and -synuclein do  ... 
doi:10.4236/jbpc.2010.11002 fatcat:zbqs6ggr5ngaxiifrnnvpqjmtq

Crosstalk Between Macroautophagy and Chaperone-Mediated Autophagy: Implications for the Treatment of Neurological Diseases

Haijian Wu, Sheng Chen, Al-Baadani Ammar, Jie Xu, Qun Wu, Kum Pan, Jianmin Zhang, Yuan Hong
2014 Molecular Neurobiology  
Macroautophagy serves as a backup mechanism to removal of malfunctioning proteins (i.e., aberrant α-synuclein) from the cytoplasm when CMA is compromised, and vice versa.  ...  Macroautophagy and chaperone-mediated autophagy (CMA) are two important subtypes of autophagy that play a critical role in cellular quality control under physiological and pathological conditions.  ...  Acknowledgments of Funding  ... 
doi:10.1007/s12035-014-8933-0 pmid:25330936 pmcid:PMC4586010 fatcat:luto363e7rdq5jurd2od6m3hfu
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