Skip to main content

Advertisement

SpringerLink
Log in

Interplay between α-synuclein and parkin genes: Insights of Parkinson’s disease

  • Review
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Parkinson’s disease (PD) is a complex and debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. The pathogenesis of PD is intimately linked to the roles of two key molecular players, α-synuclein (α-syn) and Parkin. Understanding the intricate interplay between α-syn and Parkin is essential for unravelling the molecular underpinnings of PD. Their roles in synaptic function and protein quality control underscore their significance in neuronal health. Dysregulation of these processes, as seen in PD, highlights the potential for targeted therapeutic strategies aimed at restoring normal protein homeostasis and mitigating neurodegeneration. Investigating the connections between α-syn, Parkin, and various pathological mechanisms provides insights into the complex web of factors contributing to PD pathogenesis and offers hope for the development of more effective treatments for this devastating neurological disorder. The present compilation provides an overview of their structures, regional and cellular locations, associations, physiological functions, and pathological roles in the context of PD.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

AFM:

Atomic Force Microscopy

CD:

circular dichroism

DA:

Dopamine

DAT:

Dopamine Transporter

ER:

Endoplasmic Reticulum

FRET:

fluorescence resonance energy transfer

GSK-3β:

Glycogen Synthase Kinase-3β

IBR:

In-Between RING

iNOS:

inducible Nitric Oxide Synthase

NAC:

non- amyloid -β component

NF-kB:

Nuclear Factor-kappa B NMDA, N-methyl-D-aspartate

PD:

Parkinson’s disease

PD2:

Phospholipase D2

RBR:

RING-between-RING

ROS:

Reactive Oxygen Species

SN:

Subtantia nigra

SNARE:

Soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors

TGN:

trans-Golgi network

TH:

Tyrosine Hydroxylase

TNF-α:

Tumor Necrotic Factor-α

VMAT:

Vesicular Monoamine Transporter

UPS:

Ubiquitin Proteasomal Sysytem

References

  1. Bartels AL, Leenders KL (2009) Parkinson’s disease: the syndrome, the pathogenesis and pathophysiology. Cortex 45(8):915–921

    Article  PubMed  Google Scholar 

  2. Moustafa AA et al (2016) Motor symptoms in Parkinson’s disease: a unified framework. Neurosci Biobehav Rev 68:727–740

    Article  PubMed  Google Scholar 

  3. Schapira AHV, Chaudhuri KR, Jenner P (2017) Non-motor features of Parkinson disease. Nat Rev Neurosci 18(7):435–450

    Article  CAS  PubMed  Google Scholar 

  4. Kawahara K et al (2008) Alpha-synuclein aggregates interfere with Parkin solubility and distribution: role in the pathogenesis of Parkinson disease. J Biol Chem 283(11):6979–6987

    Article  CAS  PubMed  Google Scholar 

  5. Yoo G, Shin YK, Lee NK (2023) The role of α-Synuclein in SNARE-mediated synaptic Vesicle Fusion. J Mol Biol 435(1):167775

    Article  CAS  PubMed  Google Scholar 

  6. Manna M, Murarka RK (2021) Polyunsaturated fatty acid modulates membrane-bound Monomeric α-Synuclein by modulating membrane microenvironment through preferential interactions. ACS Chem Neurosci 12(4):675–688

    Article  CAS  PubMed  Google Scholar 

  7. Lesage S et al (2013) G51D α-synuclein mutation causes a novel parkinsonian-pyramidal syndrome. Ann Neurol 73(4):459–471

    Article  CAS  PubMed  Google Scholar 

  8. Lunati A, Lesage S, Brice A (2018) The genetic landscape of Parkinson’s disease. Rev Neurol (Paris) 174(9):628–643

    Article  CAS  PubMed  Google Scholar 

  9. Correia Guedes L et al (2020) Are genetic and idiopathic forms of Parkinson’s disease the same disease? J Neurochem 152(5):515–522

    Article  CAS  PubMed  Google Scholar 

  10. Perfeito R, Cunha-Oliveira T, Rego AC (2013) Reprint of: revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease-resemblance to the effect of amphetamine drugs of abuse. Free Radic Biol Med 62:186–201

    Article  CAS  PubMed  Google Scholar 

  11. Sulzer D (2007) Multiple hit hypotheses for dopamine neuron loss in Parkinson’s disease. Trends Neurosci 30(5):244–250

    Article  CAS  PubMed  Google Scholar 

  12. Goedert M (1997) The awakening of α-synuclein. Nature 388(6639):232–233

    Article  CAS  PubMed  Google Scholar 

  13. Breydo L, Wu JW, Uversky VN (2012) Α-synuclein misfolding and Parkinson’s disease Biochim Biophys Acta, 1822(2): pp. 261 – 85

  14. Bartels T, G Choi J, J Selkoe D (2011) α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 477(7362):107–110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ghosh D et al (2015) Structure based aggregation studies reveal the presence of helix-rich intermediate during α-Synuclein aggregation. Sci Rep 5(1):9228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Giasson BI et al (2001) A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. J Biol Chem 276(4):2380–2386

    Article  CAS  PubMed  Google Scholar 

  17. Stephens AD, Zacharopoulou M (2019) K.J.T.i.b.s. Schierle. Cell Environ Affects Monomeric α-synuclein Struct 44(5):453–466

    CAS  Google Scholar 

  18. Halliday GM, McCann H (2008) Human-based studies on alpha-synuclein deposition and relationship to Parkinson’s disease symptoms. Exp Neurol 209(1):12–21

    Article  CAS  PubMed  Google Scholar 

  19. Maroteaux L, Campanelli JT, Scheller RH (1988) Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci 8(8):2804–2815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhong SC et al (2010) Expression and subcellular location of alpha-synuclein during mouse-embryonic development. Cell Mol Neurobiol 30(3):469–482

    Article  CAS  PubMed  Google Scholar 

  21. Giasson BI et al (2001) Prominent perikaryal expression of alpha- and beta-synuclein in neurons of dorsal root ganglion and in medullary neurons. Exp Neurol 172(2):354–362

    Article  CAS  PubMed  Google Scholar 

  22. Polymeropoulos MH et al (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276(5321):2045–2047

    Article  CAS  PubMed  Google Scholar 

  23. Calo L et al (2016) Synaptic failure and α-synuclein. Mov Disord 31(2):169–177

    Article  CAS  PubMed  Google Scholar 

  24. El-Agnaf OM et al (2003) Alpha-synuclein implicated in Parkinson’s disease is present in extracellular biological fluids, including human plasma. Faseb j 17(13):1945–1947

    Article  CAS  PubMed  Google Scholar 

  25. Lee HJ, Patel S, Lee SJ (2005) Intravesicular localization and exocytosis of alpha-synuclein and its aggregates. J Neurosci 25(25):6016–6024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. McLean PJ et al (2000) Membrane association and protein conformation of alpha-synuclein in intact neurons. Effect of Parkinson’s disease-linked mutations. J Biol Chem 275(12):8812–8816

    Article  CAS  PubMed  Google Scholar 

  27. Cheng F, Vivacqua G, Yu S (2011) The role of α-synuclein in neurotransmission and synaptic plasticity. J Chem Neuroanat 42(4):242–248

    Article  CAS  PubMed  Google Scholar 

  28. Masliah E et al (2000) Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 287(5456):1265–1269

    Article  CAS  PubMed  Google Scholar 

  29. Kirik D et al (2002) Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system. J Neurosci 22(7):2780–2791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lotharius J et al (2002) Effect of mutant alpha-synuclein on dopamine homeostasis in a new human mesencephalic cell line. J Biol Chem 277(41):38884–38894

    Article  CAS  PubMed  Google Scholar 

  31. Gadhavi J et al (2022) Neurotoxic or neuroprotective: post-translational modifications of α-synuclein at the cross-roads of functions. Biochimie 192:38–50

    Article  CAS  PubMed  Google Scholar 

  32. Mizuno Y et al (2001) Parkin and Parkinson’s disease. Curr Opin Neurol 14(4):477–482

    Article  CAS  PubMed  Google Scholar 

  33. Fakih R, Sauvé V, Gehring K (2022) Structure of the second phosphoubiquitin-binding site in parkin. J Biol Chem 298(7):102114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Beasley SA, Hristova VA, Shaw GS (2007) Structure of the parkin in-between-ring domain provides insights for E3-ligase dysfunction in autosomal recessive Parkinson’s disease. Proc Natl Acad Sci U S A 104(9):3095–3100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Seirafi M, Kozlov G, Gehring K (2015) Parkin structure and function. Febs j 282(11):2076–2088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. van der Reijden BA et al (1999) TRIADs: a new class of proteins with a novel cysteine-rich signature. Protein Sci 8(7):1557–1561

    Article  PubMed  PubMed Central  Google Scholar 

  37. Imai Y, Soda M, Takahashi R (2000) Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J Biol Chem 275(46):35661–35664

    Article  CAS  PubMed  Google Scholar 

  38. Kubo SI et al (2001) Parkin is associated with cellular vesicles. J Neurochem 78(1):42–54

    Article  CAS  PubMed  Google Scholar 

  39. Horowitz JM et al (1999) Identification and distribution of Parkin in rat brain. NeuroReport 10(16):3393–3397

    Article  CAS  PubMed  Google Scholar 

  40. Horowitz JM et al (2001) Immunodetection of Parkin protein in vertebrate and invertebrate brains: a comparative study using specific antibodies. J Chem Neuroanat 21(1):75–93

    Article  CAS  PubMed  Google Scholar 

  41. Kitada T et al (2000) Molecular cloning, gene expression, and identification of a splicing variant of the mouse parkin gene. Mamm Genome 11(6):417–421

    Article  CAS  PubMed  Google Scholar 

  42. Kühn K et al (2004) Parkin expression in the developing mouse. Brain Res Dev Brain Res 149(2):131–142

    Article  PubMed  Google Scholar 

  43. Ledesma MD et al (2002) Astrocytic but not neuronal increased expression and redistribution of parkin during unfolded protein stress. J Neurochem 83(6):1431–1440

    Article  CAS  PubMed  Google Scholar 

  44. Sassone J et al (2017) The synaptic function of parkin. Brain 140(9):2265–2272

    Article  PubMed  Google Scholar 

  45. Jiang H et al (2012) Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells. Nat Commun 3(1):668

    Article  PubMed  Google Scholar 

  46. Maraschi A et al (2014) Parkin regulates kainate receptors by interacting with the GluK2 subunit. Nat Commun 5:5182

    Article  CAS  PubMed  Google Scholar 

  47. Palacino JJ et al (2004) Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 279(18):18614–18622

    Article  CAS  PubMed  Google Scholar 

  48. Sarraf SA et al (2019) PINK1/Parkin influences cell cycle by sequestering TBK1 at Damaged Mitochondria, inhibiting mitosis. Cell Rep 29(1):225–235e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Takahashi R et al (2003) Parkin and endoplasmic reticulum stress. Ann N Y Acad Sci 991:101–106

    Article  CAS  PubMed  Google Scholar 

  50. Storz G, Imlay JA (1999) Oxidative stress. Curr Opin Microbiol 2(2):188–194

    Article  CAS  PubMed  Google Scholar 

  51. Hsu LJ et al (2000) alpha-synuclein promotes mitochondrial deficit and oxidative stress Am J Pathol, 157(2): pp. 401 – 10

  52. Yang YX, Muqit MM, Latchman DS (2006) Induction of parkin expression in the presence of oxidative stress. Eur J Neurosci 24(5):1366–1372

    Article  PubMed  Google Scholar 

  53. Shen J, Cookson MR (2004) Mitochondria and dopamine: new insights into recessive parkinsonism. Neuron 43(3):301–304

    Article  CAS  PubMed  Google Scholar 

  54. Liu ZQ et al (2021) Manganese-induced alpha-synuclein overexpression aggravates mitochondrial damage by repressing PINK1/Parkin-mediated mitophagy. Food Chem Toxicol 152:112213

    Article  CAS  PubMed  Google Scholar 

  55. Chaturvedi SK et al (2016) Protein misfolding and aggregation: mechanism. Factors Detect 51(9):1183–1192

    CAS  Google Scholar 

  56. Yu J, Lyubchenko YL (2009) Early stages for Parkinson’s development: alpha-synuclein misfolding and aggregation. J Neuroimmune Pharmacol 4(1):10–16

    Article  PubMed  Google Scholar 

  57. Schlehe JS et al (2008) Aberrant folding of pathogenic parkin mutants: aggregation versus degradation. J Biol Chem 283(20):13771–13779

    Article  CAS  PubMed  Google Scholar 

  58. Zheng Q et al (2016) Dysregulation of Ubiquitin-Proteasome System in neurodegenerative diseases. Front Aging Neurosci 8:303

    Article  PubMed  PubMed Central  Google Scholar 

  59. Peng X et al (2005) Alpha-synuclein activation of protein phosphatase 2A reduces tyrosine hydroxylase phosphorylation in dopaminergic cells. J Cell Sci 118(Pt 15):3523–3530

    Article  CAS  PubMed  Google Scholar 

  60. Hyman SE (2005) Neurotransmitters Curr Biol 15(5):R154–R158

    Article  CAS  PubMed  Google Scholar 

  61. Emanuele M, Chieregatti E (2015) Mechanisms of alpha-synuclein action on neurotransmission: cell-autonomous and non-cell autonomous role. Biomolecules 5(2):865–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Nemani VM et al (2010) Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 65(1):66–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Larsen KE et al (2006) Alpha-synuclein overexpression in PC12 and chromaffin cells impairs catecholamine release by interfering with a late step in exocytosis. J Neurosci 26(46):11915–11922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Itier JM et al (2003) Parkin gene inactivation alters behaviour and dopamine neurotransmission in the mouse. Hum Mol Genet 12(18):2277–2291

    Article  CAS  PubMed  Google Scholar 

  65. Cremer JN et al (2015) Changes in the expression of neurotransmitter receptors in Parkin and DJ-1 knockout mice–A quantitative multireceptor study. Neuroscience 311:539–551

    Article  CAS  PubMed  Google Scholar 

  66. Forloni G et al (2021) Inflammation and Parkinson’s disease pathogenesis: mechanisms and therapeutic insight. Prog Mol Biol Transl Sci 177:175–202

    Article  CAS  PubMed  Google Scholar 

  67. Li Y et al (2021) Targeting microglial α-synuclein/TLRs/NF-kappaB/NLRP3 inflammasome axis in Parkinson’s disease. Front Immunol 12:719807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Hoenen C et al (2016) Alpha-synuclein proteins promote pro-inflammatory cascades in microglia: stronger effects of the A53T mutant. PLoS ONE 11(9):e0162717

    Article  PubMed  PubMed Central  Google Scholar 

  69. Hoyer W et al (2004) Impact of the acidic C-terminal region comprising amino acids 109 – 140 on α-synuclein aggregation in vitro. Biochemistry 43(51):16233–16242

    Article  CAS  PubMed  Google Scholar 

  70. Hang L, Thundyil J, Lim KL (2015) Mitochondrial dysfunction and Parkinson disease: a Parkin–AMPK alliance in neuroprotection, vol 1350. Annals of the New York Academy of Sciences, pp 37–47. 1

  71. Lipton SA (2007) Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA receptor block by memantine and S-nitrosylation. Curr Drug Targets 8(5):621–632

    Article  CAS  PubMed  Google Scholar 

  72. Hedrich K et al (2004) Distribution, type, and origin of Parkin mutations: review and case studies. Mov Disorders: Official J Mov Disorder Soc 19(10):1146–1157

    Article  Google Scholar 

  73. LeWitt PA (2008) Levodopa for the treatment of Parkinson’s disease. N Engl J Med 359(23):2468–2476

    Article  CAS  PubMed  Google Scholar 

  74. Sliter DA et al (2018) Parkin and PINK1 mitigate STING-induced inflammation. Nature 561(7722):258–262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Sarkar S et al (2017) Mitochondrial impairment in microglia amplifies NLRP3 inflammasome proinflammatory signaling in cell culture and animal models of Parkinson’s disease. Npj Parkinson’s Disease 3(1):30

    Article  PubMed  PubMed Central  Google Scholar 

  76. Zhao H et al (2021) Neuroprotective role of akt in Hypoxia Adaptation in Andeans. Front NeuroSci 14:607711

    Article  PubMed  PubMed Central  Google Scholar 

  77. Reed JC (2000) Mechanisms of apoptosis. Am J Pathol 157(5):1415–1430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Smith WW et al (2005) Endoplasmic reticulum stress and mitochondrial cell death pathways mediate A53T mutant alpha-synuclein-induced toxicity. Hum Mol Genet 14(24):3801–3811

    Article  CAS  PubMed  Google Scholar 

  79. Kuroda Y et al (2006) Parkin affects mitochondrial function and apoptosis in neuronal and myogenic cells. Biochem Biophys Res Commun 348(3):787–793

    Article  CAS  PubMed  Google Scholar 

  80. Uzman A (2003) Molecular biology of the cell: Alberts. John Wiley & Sons Inc. USA, Walter, P., K., and

  81. de Oliveira GAP, Silva JL (2019) Alpha-synuclein stepwise aggregation reveals features of an early onset mutation in Parkinson’s disease. Commun Biology 2(1):374

    Article  Google Scholar 

  82. Appel-Cresswell S et al (2013) Alpha‐synuclein p. H50Q, a novel pathogenic mutation for Parkinson’s disease. 28(6):811–813

  83. Guerrero-Ferreira R et al (2019) Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy. 8:e48907

  84. Pedersen CC et al (2021) A systematic review of associations between common SNCA variants and clinical heterogeneity in Parkinson’s disease. Npj Parkinson’s Disease 7(1):54

    Article  PubMed  PubMed Central  Google Scholar 

  85. Pan F et al (2012) SNP rs356219 of the α-synuclein (SNCA) gene is associated with Parkinson’s disease in a Chinese Han population. Parkinsonism Relat Disord 18:632–634

    Article  PubMed  Google Scholar 

  86. Sriram SR et al (2005) Familial-associated mutations differentially disrupt the solubility, localization, binding and ubiquitination properties of parkin. 14(17):2571–2586

  87. Beasley SA, Hristova VA (2007) S.J.P.o.t.N.A.o.S. Shaw, Structure of the Parkin in-between-ring domain provides insights for E3-ligase dysfunction in autosomal recessive Parkinson’s disease. 104(9):3095–3100

  88. Fiesel FC et al (2015) Structural and functional impact of parkinson disease-associated mutations in the E3 ubiquitin ligase parkin. 36(8):774–786

  89. Terreni L et al (2001) New mutation (R42P) of the parkin gene in the ubiquitinlike domain associated with parkinsonism. Neurology 56(4):463–466

    Article  CAS  PubMed  Google Scholar 

  90. Liu W et al (2009) PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and α-synuclein aggregation. cell Cult Models Parkinson’s Disease 4(2):e4597

    Google Scholar 

  91. Biswas R, Bagchi AJG (2017) A comprehensive computational study on pathogenic mis-sense mutations spanning the RING2 and REP domains of Parkin protein. 610:49–58

  92. Gao T et al (2020) Association of ZNF184, IL1R2, LRRK2, ITPKB, and PARK16 with sporadic Parkinson’s disease in Eastern China. Neurosci Lett 735:135261

    Article  CAS  PubMed  Google Scholar 

  93. Chai C, Lim KL (2013) Genetic insights into sporadic Parkinson’s disease pathogenesis. Curr Genomics 14(8):486–501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Kumaran R, Cookson MR (2015) Pathways to parkinsonism redux: convergent pathobiological mechanisms in genetics of Parkinson’s disease. Hum Mol Genet 24(R1):R32–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Wilkaniec A et al (2019) Extracellular alpha-synuclein oligomers induce parkin S-Nitrosylation: relevance to sporadic Parkinson’s Disease Etiopathology. Mol Neurobiol 56(1):125–140

    Article  CAS  PubMed  Google Scholar 

  96. Choi P et al (2001) Co-association of parkin and alpha-synuclein. NeuroReport 12(13):2839–2843

    Article  CAS  PubMed  Google Scholar 

  97. Khandelwal PJ et al (2010) Parkinson-related parkin reduces α-Synuclein phosphorylation in a gene transfer model. Mol Neurodegener 5:47

    Article  PubMed  PubMed Central  Google Scholar 

  98. Jęśko H, Lenkiewicz AM, Adamczyk A (2017) Treatments and compositions targeting α-synuclein: a patent review (2010–2016). Expert Opin Ther Pat 27(4):427–438

    Article  PubMed  Google Scholar 

  99. Jęśko H et al (2019) The interplay between parkin and alpha-synuclein; possible implications for the pathogenesis of Parkinson’s disease. Acta Neurobiol Exp (Wars) 79(3):276–289

    Article  PubMed  Google Scholar 

  100. Singh K et al (2018) Parkin targets NOD2 to regulate astrocyte endoplasmic reticulum stress and inflammation. Glia 66(11):2427–2437

    Article  PubMed  PubMed Central  Google Scholar 

  101. Moszczynska A et al (2007) Parkin disrupts the alpha-synuclein/dopamine transporter interaction: consequences toward dopamine-induced toxicity. J Mol Neurosci 32(3):217–227

    Article  CAS  PubMed  Google Scholar 

  102. Chung E et al (2020) Intracellular delivery of Parkin rescues neurons from accumulation of damaged mitochondria and pathological α-synuclein. Sci Adv 6(18):eaba1193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Paciello O et al (2006) Parkin and its association with alpha-synuclein and AbetaPP in inclusion-body myositis and AbetaPP-overexpressing cultured human muscle fibers. Acta Myol 25(1):13–22

    CAS  PubMed  Google Scholar 

  104. Chung KK et al (2001) Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med 7(10):1144–1150

    Article  CAS  PubMed  Google Scholar 

  105. Shimura H et al (2001) Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson’s disease. Science 293(5528):263–269

    Article  CAS  PubMed  Google Scholar 

  106. Madsen DA et al (2021) Interaction between Parkin and α-synuclein in PARK2-mediated Parkinson’s disease. 10(2):283

  107. Twohig D, Nielsen HMJMN (2019) α-synuclein in the pathophysiology of Alzheimer’s disease. 14(1):1–19

  108. Witte ME et al (2009) Parkinson’s disease-associated parkin colocalizes with Alzheimer’s disease and multiple sclerosis brain lesions. 36(3):445–452

  109. Lücking C, Brice* AJC, CMLS MLS (2000) Alpha-synuclein Parkinson’s Disease 57:1894–1908

  110. Von Coelln R et al (2004) Parkin-associated Parkinson’s disease. 318:p175–184

  111. Lu J-Q et al (2009) Association of α-Synuclein immunoreactivity with inflammatory activity in multiple sclerosis lesions. J Neuropathology Experimental Neurol 68(2):179–189

    Article  CAS  Google Scholar 

  112. Wilhelmus MM et al (2012) Involvement and interplay of Parkin, PINK1, and DJ1 in neurodegenerative and neuroinflammatory disorders. 53(4):983–992

  113. Roberts B et al (2022) Synucleinopathy in Amyotrophic Lateral Sclerosis: A Potential Avenue for Antisense Therapeutics? 23(16): p. 9364

  114. Zhang C-W et al (2016) Parkin Regul Neurodegenerative Disorders 7:248

    Google Scholar 

  115. Charles V et al (2000) Alpha-synuclein immunoreactivity of huntingtin polyglutamine aggregates in striatum and cortex of Huntington’s disease patients and transgenic mouse models. 289(1):29–32

  116. Rubio I et al (2009) Effects of partial suppression of parkin on huntingtin mutant R6/1 mice 1281: pp. 91–100

Download references

Funding

Not applicable.

Author information

Author notes

  1. Kajal Sharma and Shivani Chib contributes equally to the manuscript.

Authors and Affiliations

  1. Department of Pharmacology, Central University of Punjab, Bathinda, 151401, India

    Kajal Sharma, Shivani Chib, Aniket Gupta, Randhir Singh & Rishabh Chalotra

Authors
  1. Kajal Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shivani Chib
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aniket Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Randhir Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rishabh Chalotra
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

K.S.: Writing–original draft. S.C.: Writing – original draft, Conceptualization. A.G.: Writing–original draft, R.S.: Writing – review & editing, Formal analysis and Supervision. R.C.: Writing–original draft. # Authors contributing equally to the manuscript (Kajal Sharma and Shivani Chib).

Corresponding author

Correspondence to Randhir Singh.

Ethics declarations

Ethical approval

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sharma, K., Chib, S., Gupta, A. et al. Interplay between α-synuclein and parkin genes: Insights of Parkinson’s disease. Mol Biol Rep 51, 586 (2024). https://doi.org/10.1007/s11033-024-09520-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11033-024-09520-7

Keywords

Search

Navigation