Oxidative Medicine and Cellular Longevity / 2015 / Article / Tab 1

Review Article

Mitochondria-Targeted Protective Compounds in Parkinson’s and Alzheimer’s Diseases

Table 1

Parkinson’s disease and mitochondria-targeted protective compounds.

CompoundClass of compoundParkinson’s modelMechanismsReferences

Acetyl-L-carnitine Quaternary ammoniumIn vitro human neuroblastoma SK-N-MC cells model of rotenone-induced PDMaintenance of mitochondrial integrity and function:
↑ mitochondrial biogenesis
↓ ROS generation
[65]

AstaxanthinNonprovitamin A carotenoidMPP(+)-induced mouse model
In vitro human neuroblastoma SK-N-SH cells model of MPP+-induced PD
Inhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax and α-synuclein
↓ caspase-3
[81]

In vitro human neuroblastoma SH-SY5Y cells model of 6-OHDA-induced PDMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential;
maintain mitochondrial redox activity
[82]
BaicaleinFlavonoidIn vitro rat adrenal pheochromocytoma PC12 cells model and isolated rat brain mitochondria of rotenone induced PDInhibition of the mitochondrial apoptotic pathway:
↓ caspase-3 and caspase-7
Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ intracellular ATP production
[83]
In vitro human neuroblastoma SH-SY5Y cells model of 6-OHDA-induced PDMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
Inhibition of the mitochondrial apoptotic pathway:
↓ caspase-3 and caspase-9
↓ p-c-Jun N-terminal kinase (JNK)
[84]

Caffeic acid
phenethyl ester
Phenolic compound6-OHDA-induced rat PD modelInhibition of the mitochondrial apoptotic pathway:
↓ caspase-3 and caspase-9
↓ cytochrome c release
Maintenance of mitochondrial integrity and function
[85]
Primary cultures of cerebellar granule neuron 6-OHDA-induced PDInhibition of the mitochondrial apoptotic pathway,
↓caspase-3
↓ cytochrome c release
[86]

CNB-001Pyrazole derivative of curcuminMPTP-induced rodent PD model Maintenance of normal mitochondrial morphology and size[87]
In vitro human neuroblastoma SK-N-SH cells model of rotenone-induced PDInhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3 and caspase-9
↓ cytochrome c release
Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
[88]

Curcumin PolyphenolPC12 cells mutant A53T α-synuclein-induced cell death Inhibition of the mitochondrial apoptotic pathway:
↓ caspase-3 and caspase-9
↓ cytochrome c release
Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
[89]
Mouse brain and the 1RB3AN27 (N27) rat dopaminergic neuronal cell line model of buthionine sulfoximine-induced PDMaintenance of mitochondrial integrity and function:
↑ activities of complex I
↓ oxidative damage to proteins
↑ glutathione
[90]

DL-3-n-butylphthalide (NBP) Synthetic compound based on L-3-n-butylphthalide In vitro rat adrenal pheochromocytoma (PC12) cells model of MPP(+)-induced PDMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ glutathione
[91]

Echinacoside Phenylethanoid glycosideIn vitro rat adrenal pheochromocytoma (PC12) cells model of H2O2-induced PDInhibition of the mitochondrial apoptotic pathway[92]

EdaravonePyrazole derivative Rotenone-induced rat PD modelInhibition of the mitochondrial apoptotic pathway:
↓ Bax
Maintenance of mitochondrial integrity and function:
↓ ROS generation
[93]

EsculetinCoumarinMPTP-induced mice PD modelInhibition of the mitochondrial apoptotic pathway:
↓ caspase-3
[94]

Ginsenoside RePanaxatriol saponinPINK1 null cellsReversing the deficit in complex IV activity:
↑ LRPPRC, Hsp90, and Hsp60 levels
[95]

Glutamoyl diester of curcuminPolyphenolMouse brain mitochondria induced-peroxynitrite PDMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
[96]

Harmalol Beta-carbolineIn vitro rat adrenal pheochromocytoma (PC12) cells model of SNAP-induced PDMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
[97]

HarmineBeta-carbolineIn vitro rat adrenal pheochromocytoma (PC12) cells model of SNAP-induced PDMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
[97]

HesperidinPolyphenolIn vitro human neuroblastoma SK-N-SH cells model of rotenone-induced PDInhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3 and caspase-9
↓ cytochrome c release
Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ glutathione
[98]

Isoborneol Monoterpenoid alcoholIn vitro human neuroblastoma SH-SY5Y cells model of 6-OHDA-induced PDInhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3
↓ cytochrome c release
[99]

KaempferolFlavonoidIn vitro human neuroblastoma SH-SY5Y cells model and primary neurons of rotenone-induced PD↑ Autophagy [100]

α-Lipoic acid Organosulfur compound derived from octanoic acidIn vitro rat adrenal pheochromocytoma PC12 cells model of MPP(+)-induced PDMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
[75]
Rotenone-induced rat PD modelMaintenance of mitochondrial integrity and function:
↑ mitochondrial complex I activity
↑ glutathione
[76]
In vitro human neuroblastoma SK-N-MC cells model of rotenone-induced PDMaintenance of mitochondrial integrity and function:
↑ mitochondrial biogenesis
↓ ROS generation
[77]
In vitro rat adrenal pheochromocytoma (PC12) cells model of PDMaintenance of mitochondrial integrity and function:
↑ mitochondrial complex I activity
↑ glutathione
[78]

Lycopene Carotenoid In vitro human neuroblastoma SH-SY5Y cells model of MPP(+)-induced PDMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↓ lipid peroxidation
↑ intracellular ATP production
↑ mitochondrial DNA copy numbers and mitochondrial RNA transcript levels
[101]
Rotenone-induced rat PD modelInhibition of the mitochondrial apoptotic pathway:
↓ cytochrome c release
Maintenance of mitochondrial integrity and function:
↓ lipid peroxidation
↑ SOD activity
↑ glutathione
[102]

MPTP-induced mice PD modelMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↑ antioxidant enzyme levels
↑ intracellular ATP production
[67]
Rotenone-induced rat PD modelMaintenance of mitochondrial integrity and function:
↓ ROS generation
↑ glutathione
↑ SOD and catalase activities
[68]
MelatoninHormoneRotenone-induced isolated rat brain mitochondria PD modelMaintenance of mitochondrial integrity and function:
↓ Ca2+ levels
↓ ROS generation
[69]
6-OHDA-induced rat PD modelMaintenance of mitochondrial integrity and function:
↑ mitochondrial complex I activity
[70]
MPP(+)-induced isolated rat liver mitochondria and striatal synaptosomes PD modelMaintenance of mitochondrial integrity and function:
↑ mitochondrial complex I activity
[71]

MitoQ (mitoquinone
mesylate)
In vitro human neuroblastoma SH-SY5Y cells model of 6-OHDA-induced PDInhibition of the mitochondrial apoptotic pathway:
↓ Bax
↓ Drp1
[73]

N-AcetylcysteineAmino acid derivativeH2O2 and toxic quinones derived from dopamine-induced rat PD modelMaintenance of mitochondrial integrity and function:
↑ mitochondrial respiratory activity
↑ Na+, K+-ATPase activity
[103]

Neuropeptide cocaine and amphetamine regulated transcript (CART) PeptideIn vitro human neuroblastoma SH-SY5Y, HEK293 cells, and cultures of cortical and hippocampal neurons of H2O2-induced PDMaintenance of mitochondrial integrity and function: protection of mitochondrial DNA (mtDNA), cellular proteins, and lipids [78]

OstholeCoumarinIn vitro rat adrenal pheochromocytoma (PC12) cells model of MPP(+)-induced PDInhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3
↓ cytochrome c release
[104]

PiperineAlkaloid6-OHDA-induced rat PD modelInhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3 and caspase-9
↓ cytochrome c release
[105]

Polyhydroxylated fullerene derivative C(60)(OH)(24) In vitro human neuroblastoma cells model of MPP(+)-induced PDMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ activities of complexes I and II
↓ oxidative damage to DNA and proteins
[106]

Protocatechuic acidPolyphenolIn vitro rat adrenal pheochromocytoma (PC12) cells model of MPP(+)-induced PDInhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ caspase-3
Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ glutathione
[107]

Pyruvate Organic acidIn vitro human neuroblastoma SK-N-SH cells model of H2O2-induced PDMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
[79]
In vitro rat adrenal pheochromocytoma (PC12) cells model of dopamine-induced PDMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↓ p53
↓ nuclear translocation of NF-kappaB
Inhibition of the mitochondrial apoptotic pathway
[80]

Quercetin Bioflavonoid Rotenone-induced rat PD modelMaintenance of mitochondrial integrity and function:
↓ ROS generation
maintain mitochondrial membrane potential
[108]
In vitro glial-neuronal system model of MPP(+)-induced PDMaintenance of mitochondrial integrity and function:
↓ inducible nitric oxide synthase protein expression
↓ superoxide radicals
[109]

RapamycinMacrolide6-OHDA-induced rat PD modelInhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-9
↓ cytochrome c release
Maintenance of mitochondrial integrity and function:
↓ lipid peroxidation
↑ SOD and GSH-PX
[110]

ResveratrolPolyphenolIn vitro primary fibroblasts cultures from patients with parkin mutations (PARK2)Maintenance of mitochondrial integrity and function:
↑ complex I activity
↑ citrate synthase activity
↑ basal oxygen consumption
↑ mitochondrial ATP production
↓ lactate content
[111]

Rosmarinic acidPolyphenolIn vitro MES23.5 dopaminergic cells model of 6-OHDA-induced PD.Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
[112]

Salvianic acid A PolyphenolIn vitro human neuroblastoma SH-SY5Y cells model of MPP(+)-induced PDInhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
[113]

Salvianolic acid BPolyphenolIn vitro human neuroblastoma SH-SY5Y cells model of 6-OHDA-induced PDInhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3
↓ cytochrome c release
[114]

SesaminLignanIn vitro glial-neuronal system model of MPP(+)-induced PDMaintenance of mitochondrial integrity and function:
↓ inducible nitric oxide synthase protein expression
↓ superoxide radicals
[22]

Tetramethylpyrazine PyrazineMPTP-induced rat PD modelInhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3
↓ cytochrome c release
[115]

Tyrosol Phenolic compoundMPP(+)-induced CATH.a cells PD modelMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential;
maintain intracellular ATP production
Inhibition of the mitochondrial apoptotic pathway:
(i) activation of PI3K/Akt signalling pathway
[116]

Umbelliferone CoumarinMPTP-induced mice PD modelInhibition of the mitochondrial apoptotic pathway:
↓ caspase-3
[94]

Ursodeoxycholic
acid
Secondary bile acidsIn vitro human neuroblastoma SH-SY5Y cells model of SNP-induced PDInhibition of the mitochondrial apoptotic pathway:
↑ Bcl-2
↓ Bax
↓ caspase-3, caspase-7, and caspase-9
↓ cytochrome c release
Maintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ glutathione
[74]

Xyloketal BTriterpenoidIn vitro rat adrenal pheochromocytoma (PC12) cells model and Caenorhabditis elegans of MPP(+)-induced PDMaintenance of mitochondrial integrity and function:
maintain mitochondrial membrane potential
↓ ROS generation
↑ glutathione
[117]