Therapeutic targeting of mitophagy in Parkinson's disease.
PTEN induced putative kinase 1
Parkin
Parkinsons disease
mitochondria
mitophagy
ubiquitin
Journal
Biochemical Society transactions
ISSN: 1470-8752
Titre abrégé: Biochem Soc Trans
Pays: England
ID NLM: 7506897
Informations de publication
Date de publication:
29 04 2022
29 04 2022
Historique:
received:
21
01
2022
revised:
04
03
2022
accepted:
07
03
2022
pubmed:
22
3
2022
medline:
3
5
2022
entrez:
21
3
2022
Statut:
ppublish
Résumé
Parkinson's disease is a neurodegenerative disorder characterised by cardinal motor symptoms and a diverse range of non-motor disorders in patients. Parkinson's disease is the fastest growing neurodegenerative condition and was described for the first time over 200 years ago, yet there are still no reliable diagnostic markers and there are only treatments that temporarily alleviate symptoms in patients. Early-onset Parkinson's disease is often linked to defects in specific genes, including PINK1 and Parkin, that encode proteins involved in mitophagy, the process of selective autophagic elimination of damaged mitochondria. Impaired mitophagy has been associated with sporadic Parkinson's and agents that damage mitochondria are known to induce Parkinson's-like motor symptoms in humans and animal models. Thus, modulating mitophagy pathways may be an avenue to treat a subset of early-onset Parkinson's disease that may additionally provide therapeutic opportunities in sporadic disease. The PINK1/Parkin mitophagy pathway, as well as alternative mitophagy pathways controlled by BNIP3L/Nix and FUNDC1, are emerging targets to enhance mitophagy to treat Parkinson's disease. In this review, we report the current state of the art of mitophagy-targeted therapeutics and discuss the approaches being used to overcome existing limitations to develop innovative new therapies for Parkinson's disease. Key approaches include the use of engineered mouse models that harbour pathogenic mutations, which will aid in the preclinical development of agents that can modulate mitophagy. Furthermore, the recent development of chimeric molecules (AUTACs) that can bypass mitophagy pathways to eliminate damaged mitochondria thorough selective autophagy offer new opportunities.
Identifiants
pubmed: 35311891
pii: 231065
doi: 10.1042/BST20211107
pmc: PMC9162468
doi:
Substances chimiques
FUNDC1 protein, mouse
0
Membrane Proteins
0
Mitochondrial Proteins
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Protein Kinases
EC 2.7.-
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
783-797Informations de copyright
© 2022 The Author(s).
Références
Dialogues Clin Neurosci. 2004 Sep;6(3):259-80
pubmed: 22033559
Biochem Soc Trans. 2020 Aug 28;48(4):1737-1750
pubmed: 32677670
Free Radic Biol Med. 2019 Mar;133:221-233
pubmed: 30266679
Elife. 2021 Aug 03;10:
pubmed: 34340748
Nat Genet. 2006 May;38(5):515-7
pubmed: 16604074
EMBO J. 2014 Feb 18;33(4):282-95
pubmed: 24446486
Nat Commun. 2017 Mar 09;8:14697
pubmed: 28276439
Science. 2018 Feb 23;359(6378):
pubmed: 29472455
Nature. 2021 Aug;596(7873):590-596
pubmed: 34293799
Nat Rev Drug Discov. 2018 Jan;17(1):57-78
pubmed: 28959952
Sci Rep. 2017 Mar 10;7:44373
pubmed: 28281653
Arch Neurol. 2003 Sep;60(9):1253-6
pubmed: 12975291
iScience. 2020 May 22;23(5):101048
pubmed: 32335362
Cancer Res. 2001 Sep 15;61(18):6669-73
pubmed: 11559532
Mov Disord. 2012 Sep 1;27(10):1299-303
pubmed: 22807239
Lancet. 2011 Feb 19;377(9766):641-9
pubmed: 21292315
J Biol Chem. 2021 Jan-Jun;296:100209
pubmed: 33372898
Neuron. 2015 Jul 15;87(2):371-81
pubmed: 26182419
Biochim Biophys Acta. 2008 Feb;1777(2):173-85
pubmed: 17996721
NPJ Parkinsons Dis. 2021 Oct 14;7(1):94
pubmed: 34650080
Nature. 2018 Sep;561(7722):258-262
pubmed: 30135585
EMBO Rep. 2017 Mar;18(3):495-509
pubmed: 28104734
J Biosci Bioeng. 2021 Dec;132(6):640-650
pubmed: 34429248
Cell Metab. 2018 Feb 6;27(2):439-449.e5
pubmed: 29337137
Nat Rev Mol Cell Biol. 2020 Apr;21(4):204-224
pubmed: 32071438
J Biol Chem. 2019 Jun 28;294(26):10300-10314
pubmed: 31110043
EMBO J. 2015 Oct 14;34(20):2492-505
pubmed: 26254305
Nature. 2021 Nov;599(7886):650-656
pubmed: 34732887
Mol Neurodegener. 2020 Mar 13;15(1):20
pubmed: 32169097
Nat Struct Mol Biol. 2017 Nov;24(11):911-919
pubmed: 28945247
J Neuropsychiatry Clin Neurosci. 2002 Spring;14(2):223-36; discussion 222
pubmed: 11983801
Pharmaceuticals (Basel). 2019 Jun 19;12(2):
pubmed: 31248150
Nature. 2014 May 1;509(7498):105-9
pubmed: 24695223
J Mol Biol. 2020 Apr 3;432(8):2510-2524
pubmed: 31689437
J Biol Chem. 2013 Dec 20;288(51):36372-84
pubmed: 24189060
Chembiochem. 2018 Mar 2;19(5):425-429
pubmed: 29226533
Neurobiol Dis. 2016 Oct;94:169-78
pubmed: 27189756
Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S74-6
pubmed: 22166461
Science. 2012 Aug 31;337(6098):1062-5
pubmed: 22936770
Arch Neurol. 2003 Jul;60(7):975-80
pubmed: 12873854
Mol Cell. 2014 May 8;54(3):362-77
pubmed: 24746696
Neuron. 2015 Jan 21;85(2):257-73
pubmed: 25611507
Antioxid Redox Signal. 2014 Jul 10;21(2):195-210
pubmed: 24251381
Mol Cell. 2020 Mar 5;77(5):1107-1123.e10
pubmed: 32142684
Nat Cell Biol. 2012 Jan 22;14(2):177-85
pubmed: 22267086
Cell. 2013 Aug 15;154(4):737-47
pubmed: 23953109
Mov Disord. 2006 Jun;21(6):789-93
pubmed: 16482571
EMBO J. 2019 Jan 15;38(2):
pubmed: 30573668
Nature. 2019 Aug;572(7770):533-537
pubmed: 31413367
Mol Cell. 2018 Apr 19;70(2):211-227.e8
pubmed: 29656925
Mol Cell. 2020 Mar 5;77(5):1124-1142.e10
pubmed: 32142685
J Med Chem. 2017 Apr 27;60(8):3518-3524
pubmed: 28323427
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
Lancet. 1989 Jun 3;1(8649):1269
pubmed: 2566813
PLoS One. 2015 Nov 10;10(11):e0142438
pubmed: 26555609
Acta Neuropathol Commun. 2020 Nov 9;8(1):189
pubmed: 33168089
Cell Rep. 2014 Nov 20;9(4):1538-53
pubmed: 25456142
Cell Death Differ. 2021 Feb;28(2):570-590
pubmed: 33414510
Antioxid Redox Signal. 2019 Jan 10;30(2):198-212
pubmed: 29402144
Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6283-8
pubmed: 22460798
Biochem Biophys Res Commun. 1989 Sep 29;163(3):1450-5
pubmed: 2551290
J Cell Biol. 2008 Dec 1;183(5):795-803
pubmed: 19029340
Hum Mol Genet. 2019 Sep 1;28(17):2811-2825
pubmed: 30994895
Cell. 2006 Jun 30;125(7):1241-52
pubmed: 16814712
Antioxid Redox Signal. 2010 Sep 15;13(6):783-96
pubmed: 20121342
Essays Biochem. 2018 Jul 20;62(3):341-360
pubmed: 30030364
Nat Struct Mol Biol. 2017 Nov;24(11):920-930
pubmed: 28945249
Nat Neurosci. 2014 Jun;17(6):832-40
pubmed: 24816140
Neurochem Int. 2017 Oct;109:106-116
pubmed: 28434973
Mol Cell. 2019 Apr 18;74(2):347-362.e6
pubmed: 30853401
Nature. 2015 Aug 20;524(7565):370-4
pubmed: 26161729
Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6400-5
pubmed: 23509287
Life Sci Alliance. 2020 Jul 7;3(8):
pubmed: 32636217
Open Biol. 2012 May;2(5):120080
pubmed: 22724072
Nat Struct Mol Biol. 2018 Jul;25(7):623-630
pubmed: 29967542
Hum Mol Genet. 2015 May 1;24(9):2528-38
pubmed: 25612572
Nature. 2013 Apr 18;496(7445):372-6
pubmed: 23503661
J Biol Chem. 2003 Mar 7;278(10):8516-25
pubmed: 12496265
Mol Cell. 2019 Dec 5;76(5):797-810.e10
pubmed: 31606272
EMBO Rep. 2022 Feb 3;23(2):e48754
pubmed: 34994490
Nature. 1998 Apr 9;392(6676):605-8
pubmed: 9560156
Nat Commun. 2020 Jan 3;11(1):88
pubmed: 31900402
Ageing Res Rev. 2014 Mar;14:19-30
pubmed: 24503004
Nature. 2014 Jun 19;510(7505):370-5
pubmed: 24896179
EMBO J. 2013 Jul 31;32(15):2099-112
pubmed: 23727886
Nat Commun. 2013;4:1982
pubmed: 23770887
Autophagy. 2020 Apr;16(4):765-766
pubmed: 31958028
Bioorg Med Chem Lett. 2018 Aug 15;28(15):2655-2659
pubmed: 29935771
Redox Biol. 2018 Apr;14:100-115
pubmed: 28888202
Nature. 2022 Feb;602(7896):328-335
pubmed: 34933320
J Neurochem. 2016 Oct;139 Suppl 1:91-107
pubmed: 26223426
Science. 1983 Feb 25;219(4587):979-80
pubmed: 6823561
Dev Cell. 2012 Feb 14;22(2):320-33
pubmed: 22280891
Proc Natl Acad Sci U S A. 2007 Jul 3;104(27):11441-6
pubmed: 17563363
BMC Biol. 2018 Jan 10;16(1):2
pubmed: 29325568
Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1325-30
pubmed: 17227870
Neurobiol Dis. 2020 Mar;136:104717
pubmed: 31846738
Autophagy. 2020 Feb;16(2):203-222
pubmed: 30945962
Biochem J. 2021 Dec 10;478(23):4099-4118
pubmed: 34704599
Autophagy. 2022 Jan 6;:1-20
pubmed: 34989313
Front Pharmacol. 2014 Feb 17;5:19
pubmed: 24596558
JCI Insight. 2020 Jun 4;5(11):
pubmed: 32493843
Mol Cell. 2022 Jan 6;82(1):44-59.e6
pubmed: 34875213
Cell Death Dis. 2019 Nov 14;10(11):865
pubmed: 31727879
Sci Rep. 2020 Jan 30;10(1):1465
pubmed: 32001742
Arch Neurol. 2006 Apr;63(4):584-8
pubmed: 16606773
Chem Commun (Camb). 2021 Dec 7;57(97):13194-13197
pubmed: 34816823
Nature. 2018 Jul;559(7714):410-414
pubmed: 29995846
EMBO Rep. 2020 Nov 5;21(11):e50202
pubmed: 32975364
Mol Cell. 2014 Nov 6;56(3):360-375
pubmed: 25284222
Curr Neurol Neurosci Rep. 2018 Apr 3;18(5):21
pubmed: 29616350
Nat Cell Biol. 2015 Feb;17(2):160-9
pubmed: 25621951
Nature. 2015 Aug 20;524(7565):309-314
pubmed: 26266977
J Biol Chem. 2003 Oct 31;278(44):43628-35
pubmed: 12930822
Neuroscience. 2011 Dec 15;198:221-31
pubmed: 21884755
Sci Adv. 2021 Apr 7;7(15):
pubmed: 33827825
Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S66-70
pubmed: 22166458
Science. 2017 Sep 22;357(6357):1255-1261
pubmed: 28882997
iScience. 2021 Dec 18;25(1):103650
pubmed: 35024585
Sci Adv. 2021 Nov 12;7(46):eabj0722
pubmed: 34767452
Nature. 2019 Jul;571(7766):565-569
pubmed: 31316206
Science. 2013 Jun 21;340(6139):1451-5
pubmed: 23661642
Sci Rep. 2017 May 3;7(1):1398
pubmed: 28469157
J Neural Transm (Vienna). 2020 Feb;127(2):159-168
pubmed: 31848775
Nature. 2008 Jul 10;454(7201):232-5
pubmed: 18454133
Environ Health Perspect. 2011 Jun;119(6):866-72
pubmed: 21269927
Brain. 2021 Apr 12;144(3):975-988
pubmed: 33543247
J Mov Disord. 2021 Jan;14(1):34-41
pubmed: 33278869
Cell Res. 2014 Apr;24(4):482-96
pubmed: 24513856
EMBO Rep. 2013 Dec;14(12):1127-35
pubmed: 24176932
Autophagy. 2013 Nov 1;9(11):1758-69
pubmed: 24121706
Nature. 2021 Feb;590(7844):57-66
pubmed: 33536648
Nat Neurosci. 2000 Dec;3(12):1301-6
pubmed: 11100151