OpenLB
Open Library of Bioscience
Advanced Search
Frontiers in neuroscience
2023;17 1244022.

Restoring autophagic function: a case for type 2 diabetes mellitus drug repurposing in Parkinson's disease.

Marco Greco, Anas Munir, Debora Musarò, Chiara Coppola, Michele Maffia
Author Information
  1. Marco Greco: Department of Biological and Environmental Science and Technology, University of Salento, Lecce, Italy.
  2. Anas Munir: Department of Biological and Environmental Science and Technology, University of Salento, Lecce, Italy.
  3. Debora Musarò: Department of Biological and Environmental Science and Technology, University of Salento, Lecce, Italy.
  4. Chiara Coppola: Department of Biological and Environmental Science and Technology, University of Salento, Lecce, Italy.
  5. Michele Maffia: Department of Biological and Environmental Science and Technology, University of Salento, Lecce, Italy.
PMID: 38027497 DOI: 10.3389/fnins.2023.1244022

Abstract

Parkinson's disease (PD) is a predominantly idiopathic pathological condition characterized by protein aggregation phenomena, whose main component is alpha-synuclein. Although the main risk factor is ageing, numerous evidence points to the role of type 2 diabetes mellitus (T2DM) as an etiological factor. Systemic alterations classically associated with T2DM like insulin resistance and hyperglycemia modify biological processes such as autophagy and mitochondrial homeostasis. High glucose levels also compromise protein stability through the formation of advanced glycation end products, promoting protein aggregation processes. The ability of antidiabetic drugs to act on pathways impaired in both T2DM and PD suggests that they may represent a useful tool to counteract the neurodegeneration process. Several clinical studies now in advanced stages are looking for confirmation in this regard.

Keywords

Parkinson’s disease alpha-synuclein autophagy hyperglycemia insulin-resistance islet amyloid peptide protein type 2 diabetes mellitus

References

  1. Neurosci Lett. 2020 Jan 1;714:134567 [PMID: 31629033]
  2. NPJ Parkinsons Dis. 2022 Jun 1;8(1):66 [PMID: 35650269]
  3. Science. 1997 Jun 27;276(5321):2045-7 [PMID: 9197268]
  4. Nat Cell Biol. 2002 Feb;4(2):160-4 [PMID: 11813001]
  5. J Biol Chem. 1979 Aug 25;254(16):7579-84 [PMID: 38243]
  6. Nat Neurosci. 2018 Oct;21(10):1341-1349 [PMID: 30258241]
  7. J Neurosci. 2003 Aug 6;23(18):7084-92 [PMID: 12904469]
  8. CNS Neurosci Ther. 2021 Mar;27(3):308-319 [PMID: 33497031]
  9. Bull Exp Biol Med. 2021 Aug;171(4):425-430 [PMID: 34542745]
  10. Int J Mol Sci. 2023 May 08;24(9): [PMID: 37176166]
  11. Cell Biochem Funct. 2022 Dec;40(8):903-913 [PMID: 36169111]
  12. Nat Rev Drug Discov. 2019 Jul;18(7):527-551 [PMID: 30867601]
  13. J Biochem Mol Toxicol. 2022 Jun;36(6):e23041 [PMID: 35343021]
  14. Sci Rep. 2022 Jan 28;12(1):1567 [PMID: 35091584]
  15. Int J Mol Sci. 2021 Mar 30;22(7): [PMID: 33808194]
  16. J Neuroendocrinol. 2016 Nov;28(11): [PMID: 27631195]
  17. Antioxid Redox Signal. 2011 Jul 1;15(1):111-22 [PMID: 20812780]
  18. J Mol Endocrinol. 2020 Apr;64(3):125-132 [PMID: 31990657]
  19. Diabetes. 2002 Oct;51(10):2944-50 [PMID: 12351431]
  20. Arch Pharm (Weinheim). 2021 Sep;354(9):e2100021 [PMID: 33988883]
  21. Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1701-1712 [PMID: 31002870]
  22. Arterioscler Thromb Vasc Biol. 2021 Apr;41(4):e208-e223 [PMID: 33535788]
  23. Biology (Basel). 2023 Apr 11;12(4): [PMID: 37106782]
  24. Redox Biol. 2023 Oct;66:102849 [PMID: 37591012]
  25. J Neurosci. 2010 Sep 15;30(37):12535-44 [PMID: 20844148]
  26. PLoS One. 2019 Apr 25;14(4):e0214364 [PMID: 31022213]
  27. Acta Neuropathol. 2018 Jun;135(6):877-886 [PMID: 29536165]
  28. World J Diabetes. 2021 Jan 15;12(1):19-46 [PMID: 33520106]
  29. Life Sci. 2023 Apr 15;319:121502 [PMID: 36796719]
  30. Adv Exp Med Biol. 2017;1037:89-95 [PMID: 29147905]
  31. Biomed Pharmacother. 2020 Oct;130:110523 [PMID: 32702632]
  32. Br J Clin Pharmacol. 2019 Jan;85(1):37-46 [PMID: 30290005]
  33. Int J Clin Pharm. 2022 Aug;44(4):852-859 [PMID: 35715543]
  34. Cell Death Dis. 2014 May 08;5:e1209 [PMID: 24810045]
  35. Arterioscler Thromb Vasc Biol. 2020 Jan;40(1):145-158 [PMID: 31747801]
  36. Diabetes Obes Metab. 2022 Dec;24(12):2353-2363 [PMID: 35848461]
  37. Neurobiol Aging. 2014 May;35(5):1111-5 [PMID: 24300239]
  38. Neuroscience. 2020 Feb 1;426:101-114 [PMID: 31846748]
  39. Neurosci Bull. 2020 Apr;36(4):346-358 [PMID: 31939095]
  40. FASEB J. 2019 Mar;33(3):4458-4472 [PMID: 30676773]
  41. Neurology. 2018 May 8;90(19):e1654-e1662 [PMID: 29626177]
  42. Diabetes Care. 2011 May;34(5):1102-8 [PMID: 21411503]
  43. Behav Brain Res. 2017 Mar 1;320:484-493 [PMID: 27773683]
  44. Proc Natl Acad Sci U S A. 2004 May 11;101(19):7281-6 [PMID: 15118080]
  45. PLoS One. 2018 Jun 7;13(6):e0198626 [PMID: 29879181]
  46. J Mov Disord. 2021 Sep;14(3):193-203 [PMID: 34399565]
  47. Front Synaptic Neurosci. 2010 Sep 22;2:139 [PMID: 21423525]
  48. Int J Mol Sci. 2021 Feb 18;22(4): [PMID: 33670800]
  49. Eur J Pharmacol. 2022 Jun 5;924:174960 [PMID: 35436474]
  50. Front Mol Neurosci. 2018 Dec 21;11:465 [PMID: 30622456]
  51. Int J Obes (Lond). 2014 Jan;38(1):148-51 [PMID: 23649472]
  52. Behav Neurosci. 1993 Dec;107(6):926-40 [PMID: 8136068]
  53. Life Sci. 2019 Oct 1;234:116776 [PMID: 31425698]
  54. J Clin Endocrinol Metab. 2020 May 1;105(5): [PMID: 31665455]
  55. J Neurosci. 2002 Apr 15;22(8):3090-9 [PMID: 11943812]
  56. J Cell Biol. 2008 Aug 25;182(4):685-701 [PMID: 18725538]
  57. Mol Neurobiol. 2017 Oct;54(8):6507-6522 [PMID: 27730514]
  58. Nature. 1967 Sep 23;215(5108):1375-6 [PMID: 6055448]
  59. Exp Clin Endocrinol Diabetes. 2023 Nov;131(11):595-604 [PMID: 37729949]
  60. Eur Neuropsychopharmacol. 2015 May;25(5):713-24 [PMID: 23642796]
  61. Oncotarget. 2017 Jul 25;8(30):48603-48618 [PMID: 28611284]
  62. Nature. 1997 Aug 28;388(6645):839-40 [PMID: 9278044]
  63. Nat Genet. 2009 Dec;41(12):1308-12 [PMID: 19915575]
  64. Behav Brain Res. 2014 Nov 1;274:390-9 [PMID: 25127682]
  65. Life Sci. 2019 Dec 15;239:117047 [PMID: 31730865]
  66. Chem Res Toxicol. 2016 Feb 15;29(2):227-34 [PMID: 26771051]
  67. Diabetes Obes Metab. 2019 Mar;21(3):700-704 [PMID: 30259623]
  68. Pharmaceuticals (Basel). 2021 Feb 05;14(2): [PMID: 33562458]
  69. Front Mol Biosci. 2020 Jun 03;7:104 [PMID: 32582762]
  70. Diabetes. 2006 May;55(5):1190-6 [PMID: 16644672]
  71. Endocrinology. 1980 Feb;106(2):619-25 [PMID: 6243542]
  72. Biochem Biophys Res Commun. 2005 Nov 11;337(1):61-7 [PMID: 16176800]
  73. Diabetes Obes Metab. 2020 Feb;22(2):141-148 [PMID: 31468642]
  74. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9103-8 [PMID: 15181200]
  75. Brain Res Dev Brain Res. 1993 Apr 16;72(2):151-8 [PMID: 8485839]
  76. J Neurochem. 2022 Aug;162(3):245-261 [PMID: 35713360]
  77. J Mol Biol. 2020 Apr 3;432(8):2651-2672 [PMID: 32061929]
  78. Front Endocrinol (Lausanne). 2023 May 08;14:1164112 [PMID: 37223013]
  79. Neuron. 2000 Jan;25(1):239-52 [PMID: 10707987]
  80. Biochim Biophys Acta. 2008 Jun;1783(6):994-1002 [PMID: 18348871]
  81. Int J Mol Sci. 2021 Sep 21;22(18): [PMID: 34576325]
  82. Cells. 2021 Nov 12;10(11): [PMID: 34831366]
  83. Eur J Neurosci. 2019 Feb;49(3):410-421 [PMID: 30070753]
  84. Drug Alcohol Depend. 2021 Apr 1;221:108614 [PMID: 33621809]
  85. Biomolecules. 2023 Jul 31;13(8): [PMID: 37627267]
  86. J Neuroimmunol. 2007 Dec;192(1-2):89-98 [PMID: 17976742]
  87. JCI Insight. 2019 Sep 19;4(18): [PMID: 31534057]
  88. Transl Res. 2021 Apr;230:44-54 [PMID: 33115637]
  89. JCI Insight. 2018 Dec 6;3(23): [PMID: 30518693]
  90. JAMA Neurol. 2018 Jan 1;75(1):9-10 [PMID: 29131880]
  91. Free Radic Res. 2019 Jul;53(7):748-757 [PMID: 31146611]
  92. Neuroscience. 1995 Aug;67(4):809-14 [PMID: 7675207]
  93. Arch Neurol. 2010 Dec;67(12):1464-72 [PMID: 20697033]
  94. Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E293-301 [PMID: 17405830]
  95. Annu Rev Genet. 2009;43:95-118 [PMID: 19659442]
  96. Mov Disord. 2012 Jul;27(8):974-9 [PMID: 22674432]
  97. Diabetol Int. 2023 Feb 18;14(3):243-251 [PMID: 37397908]
  98. Front Endocrinol (Lausanne). 2021 Apr 28;12:615409 [PMID: 33995271]
  99. Nat Med. 2023 Sep;29(9):2358-2365 [PMID: 37635157]
  100. Mol Neurobiol. 2018 Jul;55(7):5715-5726 [PMID: 29039022]
  101. J Diabetes Investig. 2020 Jan;11(1):101-109 [PMID: 31102492]
  102. J Neurosci. 2002 Oct 15;22(20):8797-807 [PMID: 12388586]
  103. Bioorg Chem. 2018 Apr;77:548-567 [PMID: 29475164]
  104. Ther Adv Endocrinol Metab. 2021 Jan 13;12:2042018820980225 [PMID: 33489086]
  105. Lab Invest. 2019 Jul;99(7):971-981 [PMID: 30760864]
  106. Diabetes Care. 2011 Dec;34(12):2614-23 [PMID: 22110170]
  107. Sci Rep. 2019 Mar 29;9(1):5389 [PMID: 30926892]
  108. Metabolism. 2021 Jan;114:154416 [PMID: 33137378]
  109. Cardiovasc Drugs Ther. 2013 Oct;27(5):371-80 [PMID: 23657563]
  110. Brain. 2017 May 1;140(5):1399-1419 [PMID: 28398476]
  111. Front Neurol. 2020 Jun 12;11:556 [PMID: 32595595]
  112. Nature. 2011 Mar 24;471(7339):508-12 [PMID: 21346761]
  113. Biochem J. 2012 Jun 15;444(3):561-71 [PMID: 22458763]
  114. Front Neurosci. 2018 Oct 23;12:756 [PMID: 30405339]
  115. Nat Cell Biol. 2018 Sep;20(9):1013-1022 [PMID: 30154567]
  116. Mol Cell Biol. 2012 Jan;32(2):309-19 [PMID: 22083962]
  117. Diabet Med. 2006 Jun;23(6):579-93 [PMID: 16759299]
  118. Int J Neurosci. 1993 Mar-Apr;69(1-4):125-30 [PMID: 8082998]
  119. Diabetes Care. 2008 Oct;31(10):2003-5 [PMID: 18599528]
  120. Cell Signal. 2014 Dec;26(12):2694-701 [PMID: 25173700]
  121. Psychiatry Res. 2021 May;299:113830 [PMID: 33677189]
  122. J Hepatol. 2023 May;78(5):1048-1062 [PMID: 36740049]
  123. J Biol Chem. 1999 Nov 5;274(45):32048-54 [PMID: 10542237]
  124. Vascul Pharmacol. 2019 Apr;115:64-68 [PMID: 30926561]
  125. Neurochem Int. 2020 Sep;138:104772 [PMID: 32464226]
  126. Carbohydr Res. 2020 Mar;489:107927 [PMID: 32062396]
  127. Cell Rep. 2020 Nov 3;33(5):108271 [PMID: 33147455]
  128. Sci Rep. 2016 Jun 10;6:27618 [PMID: 27283430]
  129. Front Neurol. 2021 Sep 22;12:648588 [PMID: 34630269]
  130. Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):E4274-83 [PMID: 25246573]
  131. Biochem Biophys Res Commun. 2022 Dec 3;632:113-121 [PMID: 36206595]
  132. J Diabetes Res. 2016;2016:4847812 [PMID: 27761470]
  133. Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12222-6 [PMID: 11050244]
  134. Neurology. 2012 May 8;78(19):1507-11 [PMID: 22539572]
  135. Diabetes Res Clin Pract. 2022 Jan;183:109119 [PMID: 34879977]
  136. J Int Med Res. 2011;39(2):358-65 [PMID: 21672339]
  137. Diabetes Ther. 2021 Jul;12(7):1901-1914 [PMID: 34075573]
  138. Int J Mol Sci. 2020 May 03;21(9): [PMID: 32375255]
  139. Sci Rep. 2019 Apr 16;9(1):6156 [PMID: 30992489]
  140. Cell Metab. 2010 Dec 1;12(6):567-79 [PMID: 21109190]
  141. Neuropharmacology. 2020 Sep 15;175:108173 [PMID: 32497590]
  142. Cell Metab. 2012 Feb 8;15(2):186-200 [PMID: 22326220]
  143. J Biol Chem. 2022 Nov;298(11):102532 [PMID: 36162508]
  144. Commun Biol. 2019 Jan 8;2:13 [PMID: 30652125]
  145. Cell. 2016 Aug 11;166(4):867-880 [PMID: 27518562]
  146. Neuropharmacology. 2017 May 1;117:238-248 [PMID: 28223210]
  147. PLoS One. 2014 Jan 21;9(1):e85781 [PMID: 24465703]
  148. J Clin Invest. 2007 Feb;117(2):387-96 [PMID: 17273556]
  149. Redox Biol. 2022 Jul;53:102342 [PMID: 35605453]
  150. J Clin Med. 2020 Jan 23;9(2): [PMID: 31979327]
  151. J Pineal Res. 2017 Sep;63(2): [PMID: 28580603]
  152. Sci Rep. 2018 Apr 26;8(1):6556 [PMID: 29700330]
  153. Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8331-6 [PMID: 15155902]
  154. Br J Pharmacol. 2008 May;154(1):226-33 [PMID: 18332857]
  155. Nat Metab. 2020 Jan;2(1):9-31 [PMID: 32694684]
  156. Nat Med. 2018 Sep;24(9):1384-1394 [PMID: 30038219]
  157. Neurosci Res. 2021 Jan;162:13-21 [PMID: 31881233]
  158. CNS Neurosci Ther. 2018 Sep;24(9):763-774 [PMID: 29691988]
  159. Brain Sci. 2018 Mar 23;8(4): [PMID: 29570693]
  160. Diabetes Obes Metab. 2023 Apr;25(4):975-984 [PMID: 36511825]
  161. Int J Mol Sci. 2021 Jun 15;22(12): [PMID: 34203830]
  162. Mol Psychiatry. 2023 Jul;28(7):2811-2825 [PMID: 37085712]
  163. J Neurochem. 1981 Mar;36(3):1050-7 [PMID: 7009787]
  164. Nat Metab. 2021 Nov;3(11):1445-1465 [PMID: 34799702]
  165. Cell Physiol Biochem. 2018;47(6):2613-2625 [PMID: 29996119]
  166. J Neurosci. 2003 Apr 1;23(7):2939-46 [PMID: 12684481]
  167. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9747-52 [PMID: 20457924]
  168. Mol Metab. 2021 Jan;43:101114 [PMID: 33166742]
  169. J Biol Chem. 1996 Nov 1;271(44):27229-32 [PMID: 8910293]
  170. J Biol Chem. 2003 May 9;278(19):17190-7 [PMID: 12598526]
  171. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8628-32 [PMID: 3317417]
  172. Braz J Med Biol Res. 2021 May 24;54(8):e10782 [PMID: 34037093]
  173. J Biol Chem. 1996 Oct 18;271(42):26194-9 [PMID: 8824267]
  174. Nat Rev Neurol. 2018 Mar;14(3):168-181 [PMID: 29377010]
  175. Acta Neuropathol Commun. 2021 Apr 8;9(1):64 [PMID: 33832546]
  176. Cell Mol Neurobiol. 2018 Jan;38(1):121-132 [PMID: 28975471]
  177. Diabetologia. 2021 May;64(5):994-1006 [PMID: 33730188]
  178. Science. 2017 Sep 22;357(6357):1255-1261 [PMID: 28882997]
  179. Cardiovasc Diabetol. 2019 Jul 30;18(1):96 [PMID: 31362743]
  180. Exp Neurol. 2004 Jul;188(1):43-51 [PMID: 15191801]
  181. Neuropharmacology. 2017 Oct;125:396-407 [PMID: 28807678]
  182. Cell Rep. 2020 Jul 14;32(2):107902 [PMID: 32668258]
  183. Biomed Pharmacother. 2021 May;137:111315 [PMID: 33561645]
  184. Endocrinology. 2003 Dec;144(12):5615-22 [PMID: 14500580]
  185. Neurobiol Dis. 2019 Apr;124:230-239 [PMID: 30448284]
  186. Int J Mol Sci. 2021 Jun 21;22(12): [PMID: 34205659]
  187. J Clin Invest. 2013 Jun;123(6):2730-6 [PMID: 23728174]
  188. Front Endocrinol (Lausanne). 2022 Sep 29;13:1012904 [PMID: 36246878]
  189. Biochimie. 2000 Apr;82(4):327-37 [PMID: 10865121]
  190. J Neurochem. 2006 Nov;99(4):1188-96 [PMID: 16981894]
  191. EMBO J. 1998 Sep 1;17(17):5085-94 [PMID: 9724644]
  192. Int J Mol Sci. 2021 Aug 10;22(16): [PMID: 34445300]
  193. J Clin Invest. 2003 Oct;112(7):1049-57 [PMID: 14523042]
Journal Article Review

Word Cloud

Created with Highcharts 10.0.0proteindiseasetype2diabetesmellitusT2DMParkinson'sPDaggregationmainalpha-synucleinfactorhyperglycemiaprocessesautophagyadvancedpredominantlyidiopathicpathologicalconditioncharacterizedphenomenawhosecomponentAlthoughriskageingnumerousevidencepointsroleetiologicalSystemicalterationsclassicallyassociatedlikeinsulinresistancemodifybiologicalmitochondrialhomeostasisHighglucoselevelsalsocompromisestabilityformationglycationendproductspromotingabilityantidiabeticdrugsactpathwaysimpairedsuggestsmayrepresentusefultoolcounteractneurodegenerationprocessSeveralclinicalstudiesnowstageslookingconfirmationregardRestoringautophagicfunction:casedrugrepurposingParkinson’sinsulin-resistanceisletamyloidpeptide

Similar Articles

Cited By