Skip to main content

Advertisement

SpringerLink
Log in

Involvement of heat shock proteins and parkin/α-synuclein axis in Parkinson’s disease

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

Abstract

Parkinson’s disease (PD) is one of the most common neurological diseases, next only to Alzheimer’s disease (AD) in terms of prevalence. It afflicts about 2–3% of individuals over 65 years old. The etiology of PD is unknown and several environmental and genetic factors are involved. From a pathological point of view, PD is characterized by the loss of dopaminergic neurons in the substantia nigra, which causes the abnormal accumulation of α-synuclein (α-syn) (a component of Lewy bodies), which subsequently interact with heat shock proteins (HSPs), leading to apoptosis. Apoptosis is a vital pathway for establishing homeostasis in body tissues, which is regulated by pro-apoptotic and anti-apoptotic factors. Recent findings have shown that HSPs, especially HSP27 and HSP70, play a pivotal role in regulating apoptosis by influencing the factors involved in the apoptosis pathway. Moreover, it has been reported that the expression of these HSPs in the nervous system is high. Apart from this finding, investigations have suggested that HSP27 and HSP70 (related to parkin) show a potent protective and anti-apoptotic impact against the damaging outcomes of mutant α-syn toxicity to nerve cells. Therefore, in this study, we aimed to investigate the relationship between these HSPs and apoptosis in patients with PD.

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

References

  1. Hayes MT (2019) Parkinson’s disease and parkinsonism. Am J Med 132(7):802–807

    Article  PubMed  Google Scholar 

  2. Mota A, Taheraghdam A, Valilo M (2019) Paraoxonase1 and its relationship with Parkinson’s disease. Brain 4:1–6

    Google Scholar 

  3. Guo J-f et al (2010) Mutation analysis of Parkin, PINK1 and DJ-1 genes in Chinese patients with sporadic early onset parkinsonism. J Neurol 257(7):1170–1175

    Article  CAS  PubMed  Google Scholar 

  4. Ball N et al (2019) Parkinson’s disease and the environment. Front Neurol 10:218

    Article  PubMed  PubMed Central  Google Scholar 

  5. Tarolli CG et al (2020) Symptom burden among individuals with Parkinson disease: a national survey. Neurology: Clin Pract 10(1):65–72

    Google Scholar 

  6. He R et al (2018) Recent advances in biomarkers for Parkinson’s disease.Frontiers in aging neuroscience, : p.305

  7. Mota A et al (2019) Association of Paraoxonse1 (PON1) Genotypes with the Activity of PON1 in Patients with Parkinson’s Disease. Acta Neurol Taiwan 28(3):66–74

    PubMed  Google Scholar 

  8. Saedi S et al (2021) Serum lipid profile of Parkinson’s disease patients: A study from the Northwest of Iran. Caspian J Intern Med 12(2):155

    PubMed  PubMed Central  Google Scholar 

  9. Savitt D, Jankovic J (2019) Targeting α-synuclein in Parkinson’s disease: progress towards the development of disease-modifying therapeutics. Drugs 79(8):797–810

    Article  CAS  PubMed  Google Scholar 

  10. Vincent BM et al (2018) Inhibiting stearoyl-CoA desaturase ameliorates α-synuclein cytotoxicity. Cell Rep 25(10):2742–2754e31

    Article  CAS  PubMed  Google Scholar 

  11. Du X-y, Xie X-x, Liu R-t (2020) The role of α-synuclein oligomers in Parkinson’s disease. Int J Mol Sci 21(22):8645

    Article  CAS  PubMed Central  Google Scholar 

  12. Gibb W, Lees A (1988) The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. J Neurol Neurosurg Psychiatry 51(6):745–752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ludtmann MH et al (2018) α-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson’s disease. Nature communications, 9(1): p. 1–16

  14. Gao X et al (2015) Human Hsp70 disaggregase reverses Parkinson’s-linked α-synuclein amyloid fibrils. Mol Cell 59(5):781–793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nishimura K et al (2011) Development of defective and persistent Sendai virus vector: a unique gene delivery/expression system ideal for cell reprogramming. J Biol Chem 286(6):4760–4771

    Article  CAS  PubMed  Google Scholar 

  16. Moloney TC et al (2014) Heat shock protein 70 reduces α-synuclein‐induced predegenerative neuronal dystrophy in the α‐synuclein viral gene transfer rat model of Parkinson’s disease. CNS Neurosci Ther 20(1):50–58

    Article  CAS  PubMed  Google Scholar 

  17. Wahabi K, Perwez A, Rizvi MA (2018) Parkin in Parkinson’s disease and cancer: a double-edged sword. Mol Neurobiol 55(8):6788–6800

    Article  CAS  PubMed  Google Scholar 

  18. Zhang C et al (2011) Parkin, a p53 target gene, mediates the role of p53 in glucose metabolism and the Warburg effect. Proceedings of the National Academy of Sciences, 108(39): p. 16259–16264

  19. Bouman L et al (2011) Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress. Cell Death & Differentiation 18(5):769–782

    Article  CAS  Google Scholar 

  20. Klinkenberg M et al (2012) Restriction of trophic factors and nutrients induces PARKIN expression. Neurogenetics 13(1):9–21

    Article  CAS  PubMed  Google Scholar 

  21. Kim K-Y et al (2011) Parkin is a lipid-responsive regulator of fat uptake in mice and mutant human cells.The Journal of clinical investigation, 121(9)

  22. Petrucelli L et al (2002) Parkin protects against the toxicity associated with mutant α-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons. Neuron 36(6):1007–1019

    Article  CAS  PubMed  Google Scholar 

  23. Takahashi R et al (2003) Parkin and endoplasmic reticulum stress. Ann N Y Acad Sci 991(1):101–106

    Article  CAS  PubMed  Google Scholar 

  24. Trempe J-F et al (2013) Structure of parkin reveals mechanisms for ubiquitin ligase activation. Science 340(6139):1451–1455

    Article  CAS  PubMed  Google Scholar 

  25. Ko HS et al (2010) Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin’s ubiquitination and protective function. Proceedings of the National Academy of Sciences, 107(38): p. 16691–16696

  26. Lazarou M et al (2013) PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding. J Cell Biol 200(2):163–172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kitada T et al (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392(6676):605–608

    Article  CAS  PubMed  Google Scholar 

  28. Offen D et al (1995) Dopamine-induced programmed cell death in mouse thymocytes. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 1268:171–1772

  29. Ohtsuka K, Suzuki T (2000) Roles of molecular chaperones in the nervous system. Brain Res Bull 53(2):141–146

    Article  CAS  PubMed  Google Scholar 

  30. Bakthisaran R, Tangirala R, Rao CM (2015) Small heat shock proteins: role in cellular functions and pathology. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics. 1854:291–3194

  31. Wu J et al (2017) Heat shock proteins and cancer. Trends Pharmacol Sci 38(3):226–256

    Article  CAS  PubMed  Google Scholar 

  32. Mymrikov EV, Seit-Nebi AS, Gusev NB (2011) Large potentials of small heat shock proteins. Physiol Rev 91(4):1123–1159

    Article  CAS  PubMed  Google Scholar 

  33. Fan X et al (2021) Expression, Rapid Purification and Functional Analysis of DnaK from Rhodococcus ruber. Protein Pept Lett 28(9):1023–1032

    Article  CAS  PubMed  Google Scholar 

  34. Taylor IR et al (2018) The disorderly conduct of Hsc70 and its interaction with the Alzheimer’s-related Tau protein. J Biol Chem 293(27):10796–10809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ni M, Lee AS (2007) ER chaperones in mammalian development and human diseases. FEBS Lett 581(19):3641–3651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Egorin MJ et al (2001) Plasma pharmacokinetics and tissue distribution of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) in CD2F1 mice1. Cancer chemotherapy and pharmacology. 47:291–3024

  37. McClellan AJ, Scott MD, Frydman J (2005) Folding and quality control of the VHL tumor suppressor proceed through distinct chaperone pathways. Cell 121(5):739–748

    Article  CAS  PubMed  Google Scholar 

  38. Aridon P et al (2011) Protective role of heat shock proteins in Parkinson’s disease. Neurodegenerative Dis 8(4):155–168

    Article  CAS  Google Scholar 

  39. Nakamoto H, Vigh L (2007) The small heat shock proteins and their clients. Cell Mol Life Sci 64(3):294–306

    Article  CAS  PubMed  Google Scholar 

  40. Fattah A et al (2020) Dysregulation of body antioxidant content is related to initiation and progression of Parkinson’s disease. Neurosci Lett 736:135297

    Article  CAS  PubMed  Google Scholar 

  41. Macario AJ, de Macario EC (2005) Sick chaperones, cellular stress, and disease. N Engl J Med 353(14):1489–1501

    Article  CAS  PubMed  Google Scholar 

  42. Kampinga HH, Bergink S (2016) Heat shock proteins as potential targets for protective strategies in neurodegeneration. Lancet Neurol 15(7):748–759

    Article  CAS  PubMed  Google Scholar 

  43. Keifman E et al (2019) Optostimulation of striatonigral terminals in substantia nigra induces dyskinesia that increases after L-DOPA in a mouse model of Parkinson’s disease. Br J Pharmacol 176(13):2146–2161

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Davie CA (2008) A review of Parkinson’s disease. Br Med Bull 86(1):109–127

    Article  CAS  PubMed  Google Scholar 

  45. Goedert M (1999) Filamentous nerve cell inclusions in neurodegenerative diseases: tauopathies and alpha-synucleinopathies. Philosophical transactions of the royal society of london. Ser B: Biol Sci 354(1386):1101–1118

    CAS  Google Scholar 

  46. Trojanowski JQ et al (1998) Fatal attractions: abnormal protein aggregation and neuron death in Parkinson’s disease and Lewy body dementia. Cell Death & Differentiation 5(10):832–837

    Article  CAS  Google Scholar 

  47. Outeiro TF et al (2008) Formation of toxic oligomeric α-synuclein species in living cells. PLoS ONE 3(4):e1867

    Article  PubMed  PubMed Central  Google Scholar 

  48. Putcha P et al (2010) Brain-permeable small-molecule inhibitors of Hsp90 prevent α-synuclein oligomer formation and rescue α-synuclein-induced toxicity. J Pharmacol Exp Ther 332(3):849–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Savitskaya M, Onishchenko G (2015) Mechanisms of apoptosis. Biochem (Moscow) 80(11):1393–1405

    Article  CAS  Google Scholar 

  50. Erekat NS (2018) Apoptosis and its Role in Parkinson’s Disease. Exon Publications, pp 65–82

  51. Green DR (2000) Apoptotic pathways: paper wraps stone blunts scissors. Cell 102(1):1–4

    Article  CAS  PubMed  Google Scholar 

  52. Kroemer G, Tolkovsky A, Zakeri Z (2008) Elan vital, elan letal: one life but multiple deaths. Cell Death & Differentiation 15(7):1089–1090

    Article  CAS  Google Scholar 

  53. Mancini M et al (2000) Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis. J Cell Biol 149(3):603–612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ferri KF, Kroemer G (2001) Organelle-specific initiation of cell death pathways. Nat Cell Biol 3(11):E255–E263

    Article  CAS  PubMed  Google Scholar 

  55. Kurz T et al (2008) Lysosomes in iron metabolism, ageing and apoptosis. Histochem Cell Biol 129(4):389–406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bras M, Queenan B, Susin S (2005) Programmed cell death via mitochondria: different modes of dying. Biochem (Moscow) 70(2):231–239

    Article  CAS  Google Scholar 

  57. Yamamuro A et al (2011) Caspase-4 directly activates caspase-9 in endoplasmic reticulum stress–induced apoptosis in SH-SY5Y cells.Journal of pharmacological sciences, : p.1101240503–1101240503

  58. Rosati E et al (2010) Novel targets for endoplasmic reticulum stress-induced apoptosis in B-CLL. Blood. J Am Soc Hematol 116(15):2713–2723

    CAS  Google Scholar 

  59. Castedo M et al (2004) Cell death by mitotic catastrophe: a molecular definition. Oncogene 23(16):2825–2837

    Article  CAS  PubMed  Google Scholar 

  60. Zhang L, Yu J (2013) Role of apoptosis in colon cancer biology, therapy, and prevention. Curr colorectal cancer Rep 9(4):331–340

    Article  Google Scholar 

  61. Chipuk JE et al (2010) The BCL-2 family reunion. Mol Cell 37(3):299–310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Tait SW, Green DR (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 11(9):621–632

    Article  CAS  PubMed  Google Scholar 

  63. Lopez J, Tait S (2015) Mitochondrial apoptosis: killing cancer using the enemy within. Br J Cancer 112(6):957–962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Hirsova P, Gores GJ (2015) Death receptor-mediated cell death and proinflammatory signaling in nonalcoholic steatohepatitis. Cell Mol Gastroenterol Hepatol 1(1):17–27

    Article  PubMed  Google Scholar 

  65. Guicciardi M et al (2013) Apoptosis and necrosis in the liver. Compr Physiol 3: 977–1010. John Wiley & Sons Inc PubMed Google Scholar

  66. Hartmann A et al (2001) Caspase-8 is an effector in apoptotic death of dopaminergic neurons in Parkinson’s disease, but pathway inhibition results in neuronal necrosis. J Neurosci 21(7):2247–2255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Wilson G et al (2017) Good enough practices in scientific computing. PLoS Comput Biol 13(6):e1005510

    Article  PubMed  PubMed Central  Google Scholar 

  68. Garrido C, Solary E (2003) A role of HSPs in apoptosis through” protein triage”? Cell Death Differ 10(6):619

    Article  CAS  PubMed  Google Scholar 

  69. Koegl M et al (1999) A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly. Cell 96(5):635–644

    Article  CAS  PubMed  Google Scholar 

  70. Garrido C et al (2001) Heat shock proteins: endogenous modulators of apoptotic cell death. Biochem Biophys Res Commun 286(3):433–442

    Article  CAS  PubMed  Google Scholar 

  71. Imai Y et al (2002) CHIP is associated with Parkin, a gene responsible for familial Parkinson’s disease, and enhances its ubiquitin ligase activity. Mol Cell 10(1):55–67

    Article  CAS  PubMed  Google Scholar 

  72. Ban HS et al (2019) Epigenetic alterations of heat shock proteins (HSPs) in cancer. Int J Mol Sci 20(19):4758

    Article  CAS  PubMed Central  Google Scholar 

  73. Tytell M (2005) Release of heat shock proteins (Hsps) and the effects of extracellular Hsps on neural cells and tissues. Int J Hyperth 21(5):445–455

    Article  CAS  Google Scholar 

  74. Jones DR, Moussaud S, McLean P (2014) Targeting heat shock proteins to modulate α-synuclein toxicity. Ther Adv Neurol Disord 7(1):33–51

    Article  PubMed  PubMed Central  Google Scholar 

  75. Zourlidou A, Payne Smith MD, Latchman DS (2004) HSP27 but not HSP70 has a potent protective effect against α-synuclein‐induced cell death in mammalian neuronal cells. J Neurochem 88(6):1439–1448

    Article  CAS  PubMed  Google Scholar 

  76. Outeiro TF et al (2006) Small heat shock proteins protect against α-synuclein-induced toxicity and aggregation. Biochem Biophys Res Commun 351(3):631–638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Garrido C et al (2003) HSP27 and HSP70: potentially oncogenic apoptosis inhibitors. Cell Cycle 2(6):578–583

    Article  Google Scholar 

  78. Concannon CG, Orrenius S, Samali A (2001) Hsp27 inhibits cytochrome c-mediated caspase activation by sequestering both pro-caspase-3 and cytochrome c. Gene Expression The Journal of Liver Research 9(4–5):195–201

    Article  CAS  Google Scholar 

  79. Wyttenbach A et al (2002) Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin. Hum Mol Genet 11(9):1137–1151

    Article  CAS  PubMed  Google Scholar 

  80. Rogalla T et al (1999) Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor α by phosphorylation. J Biol Chem 274(27):18947–18956

    Article  CAS  PubMed  Google Scholar 

  81. Charette SJ et al (2000) Inhibition of Daxx-mediated apoptosis by heat shock protein 27. Mol Cell Biol 20(20):7602–7612

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Cardone MH et al (1998) Regulation of cell death protease caspase-9 by phosphorylation. Science 282(5392):1318–1321

    Article  CAS  PubMed  Google Scholar 

  83. Nidai Ozes O et al (1999) NF-κB activation by tumour necrosis factor requires the Akt serine–threonine kinase. Nature 401(6748):82–85

    Article  Google Scholar 

  84. Parcellier A et al (2003) Heat shock proteins, cellular chaperones that modulate mitochondrial cell death pathways. Biochem Biophys Res Commun 304(3):505–512

    Article  CAS  PubMed  Google Scholar 

  85. Mosser DD et al (2000) The chaperone function of hsp70 is required for protection against stress-induced apoptosis. Mol Cell Biol 20(19):7146–7159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Beere HM et al (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat Cell Biol 2(8):469–475

    Article  CAS  PubMed  Google Scholar 

  87. Ravagnan L et al (2001) Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nat Cell Biol 3(9):839–843

    Article  CAS  PubMed  Google Scholar 

  88. Park H-S et al (2001) Hsp72 functions as a natural inhibitory protein of c-Jun N-terminal kinase. EMBO J 20(3):446–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Meriin AB et al (1999) Protein-damaging stresses activate c-Jun N-terminal kinase via inhibition of its dephosphorylation: a novel pathway controlled by HSP72. Mol Cell Biol 19(4):2547–2555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Jolly C, Morimoto RI (2000) Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst 92(19):1564–1572

    Article  CAS  PubMed  Google Scholar 

  91. Song J, Takeda M, Morimoto RI (2001) Bag1–Hsp70 mediates a physiological stress signalling pathway that regulates Raf-1/ERK and cell growth. Nat Cell Biol 3(3):276–282

    Article  CAS  PubMed  Google Scholar 

  92. Ko S-K et al (2015) A small molecule inhibitor of ATPase activity of HSP70 induces apoptosis and has antitumor activities. Chem Biol 22(3):391–403

    Article  CAS  PubMed  Google Scholar 

  93. Zhang C-W et al (2016) Pharmacological or genetic activation of Hsp70 protects against loss of Parkin function. Neurodegenerative Dis 16(5–6):304–316

    Article  CAS  Google Scholar 

  94. Bruinsma IB et al (2011) Inhibition of α-synuclein aggregation by small heat shock proteins. Proteins: Structure, Function, and Bioinformatics, 79(10): p. 2956–2967

  95. Jia C et al (2019) Different heat shock proteins bind α-Synuclein with distinct mechanisms and synergistically prevent its amyloid aggregation. Front NeuroSci 13:1124

    Article  PubMed  PubMed Central  Google Scholar 

  96. Hasegawa T et al (2018) DnaJ/Hsp40 family and Parkinson’s disease. Front NeuroSci 11:743

    Article  PubMed  PubMed Central  Google Scholar 

  97. McLean PJ et al (2002) TorsinA and heat shock proteins act as molecular chaperones: suppression of α-synuclein aggregation. J Neurochem 83(4):846–854

    Article  CAS  PubMed  Google Scholar 

  98. Krüger R et al (1998) AlaSOPro mutation in the gene encoding α-synuclein in Parkinson’s disease. Nat Genet 18(2):106–108

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  100. Junn E, Mouradian MM (2002) Human α-synuclein over-expression increases intracellular reactive oxygen species levels and susceptibility to dopamine. Neurosci Lett 320(3):146–150

    Article  CAS  PubMed  Google Scholar 

  101. Seo JH et al (2002) α-Synuclein regulates neuronal survival via Bcl‐2 family expression and PI3/Akt kinase pathway. FASEB J 16(13):1–20

    Article  Google Scholar 

  102. Machida Y et al (2005) Common anti-apoptotic roles of parkin and α-synuclein in human dopaminergic cells. Biochem Biophys Res Commun 332(1):233–240

    Article  CAS  PubMed  Google Scholar 

  103. Kawamoto Y et al (2002) 14-3-3 proteins in Lewy bodies in Parkinson disease and diffuse Lewy body disease brains. J Neuropathology Experimental Neurol 61(3):245–253

    Article  CAS  Google Scholar 

  104. Yasuda T, Mochizuki H (2010) The regulatory role of α-synuclein and parkin in neuronal cell apoptosis; possible implications for the pathogenesis of Parkinson’s disease. Apoptosis 15(11):1312–1321

    Article  CAS  PubMed  Google Scholar 

  105. Jackson PK et al (2000) The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases. Trends Cell Biol 10(10):429–439

    Article  CAS  PubMed  Google Scholar 

  106. Joazeiro CA, Weissman AM (2000) RING finger proteins: mediators of ubiquitin ligase activity. Cell 102(5):549–552

    Article  CAS  PubMed  Google Scholar 

  107. Imai Y et al (2001) An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell 105(7):891–902

    Article  CAS  PubMed  Google Scholar 

  108. Mori H et al (1998) Pathologic and biochemical studies of juvenile parkinsonism linked to chromosome 6q. Neurology 51(3):890–892

    Article  CAS  PubMed  Google Scholar 

  109. Hayashi S et al (2000) An autopsy case of autosomal-recessive juvenile parkinsonism with a homozygous exon 4 deletion in the parkin gene. Mov Disord 15(5):884–888

    Article  CAS  PubMed  Google Scholar 

  110. Periquet M et al (2003) Parkin mutations are frequent in patients with isolated early-onset parkinsonism. Brain 126(6):1271–1278

    Article  PubMed  Google Scholar 

  111. Da Costa CA et al (2009) Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson’s disease. Nat Cell Biol 11(11):1370–1375

    Article  PubMed  PubMed Central  Google Scholar 

  112. Ren Y et al (2009) Parkin protects dopaminergic neurons against microtubule-depolymerizing toxins by attenuating microtubule-associated protein kinase activation. J Biol Chem 284(6):4009–4017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Hunot S et al (2004) JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson’s disease. Proceedings of the National Academy of Sciences, 101(2): p. 665–670

  114. Fallon L et al (2006) A regulated interaction with the UIM protein Eps15 implicates parkin in EGF receptor trafficking and PI (3) K–Akt signalling. Nat Cell Biol 8(8):834–842

    Article  CAS  PubMed  Google Scholar 

  115. Henn IH et al (2007) Parkin mediates neuroprotection through activation of IκB kinase/nuclear factor-κB signaling. J Neurosci 27(8):1868–1878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Kim SJ et al (2003) Parkin cleaves intracellular α-synuclein inclusions via the activation of calpain. J Biol Chem 278(43):41890–41899

    Article  CAS  PubMed  Google Scholar 

  117. Farrer M et al (2001) Lewy bodies and parkinsonism in families with parkin mutations. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 50(3):293–300

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the Tabriz University of Medical Sciences and Tabriz University for all support of this research.

Funding

Authors declare that the study has no fund.

Author information

Authors and Affiliations

  1. Department of biology, Islamic Azad University, Tabriz, Iran

    Nina Aghazadeh

  2. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Elmira Aboutalebi Vand Beilankouhi

  3. Research Institute for Neuroscience, Kerman University of Medical Sciences, Kerman, Iran

    Farima Fakhri

  4. Faculty of Medicine, Imamreza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran

    Morad Kohandel Gargari

  5. Department of Clinical Biochemistry, Zanjan University of Medical Sciences, Zanjan, Iran

    Parisa Bahari

  6. Department of Clinical Biochemistry and Medical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Aliasghar Moghadami & Mohammad Valilo

  7. Department of Biology, Faculty of Science, Urmia University, Urmia, Iran

    Zhila Khodabandeh

Authors
  1. Nina Aghazadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elmira Aboutalebi Vand Beilankouhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Farima Fakhri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Morad Kohandel Gargari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Parisa Bahari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aliasghar Moghadami
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhila Khodabandeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohammad Valilo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Nina Aghazadeh and Elmira Aboutalebi Vand Beilankouhi were involved in writing the article. Farima Fakhri and Morad Kohandel Gargari were involved revising and language and grammar editing. Parisa Baharii was involved in drawing the figures. Zhila Khodabandeh and Aliasghar Moghadami were involved in data collecting. Mohammad Valilo participated in the study design.

Corresponding author

Correspondence to Mohammad Valilo.

Ethics declarations

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

The authors declare no potential conflict of interest with respect to research, authorship, and/or publication of this article.

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 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

Aghazadeh, N., Beilankouhi, E.A.V., Fakhri, F. et al. Involvement of heat shock proteins and parkin/α-synuclein axis in Parkinson’s disease. Mol Biol Rep 49, 11061–11070 (2022). https://doi.org/10.1007/s11033-022-07900-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-022-07900-5

Keywords

Search

Navigation