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*2,3,4Portugal 1,5Latvia* 

**Targeting the Mitochondria by Novel** 

Maria S. Santos3, Catarina R. Oliveira4, Imanta Bruvere5,

*3CNC, Department of Life Sciences, University of Coimbra, Coimbra* 

Linda Klimaviciusa1, Maria A. S. Fernandes2, Nelda Lencberga1, Marta Pavasare1, Joaquim A. F. Vicente2, António J. M. Moreno2,

*1Department of Pharmacology, Faculty of Medicine, University of Latvia, Riga 2IMAR-CMA, Department of Life Sciences, University of Coimbra, Coimbra* 

Mitochondria are important regulators of cellular functions and energy metabolism, therefore mitochondrial dysfunction leads to a compromised energy-generating system, deteriorated cellular homeostasis and neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease (Shapira, 1999; 2009). Hence, the protection of mitochondria, even their repair mechanisms at the level of complex I, may be a key strategy in limiting mitochondrial damage and ensuring cellular integrity (Dawson Dawson, 2003). Thus, in addition to traditionally used antiparkinsonian drugs, which are focused on the activation of the dopaminergic system, different mitochondria-protecting agents are being used in clinics for the treatment of Parkinson's disease. For instance, agents with antioxidant properties, such as melatonin (Esposito & Cuzzocrea, 2010), coenzyme Q10 and creatine (Kones, 2010), lipoic acid (De Araújo et al., 2011), and the extract of Hyoscyamus niger seeds

Recently, antihypertensive drugs of the calcium antagonistic series, which belong to 1,4 dihydropyridine (DHP) class and are capable of penetrating the blood-brain barrier (e.g., nifedipine, nimodipine), were shown to significantly reduce the risk of developing Parkinson's disease (Becker et al., 2008; Ritz et al., 2010). This was explained by blocking Ltype calcium channels in the dopaminergic neurons of the substantia nigra, where elevated calcium ion concentrations initiate cell death (Sulzeret & Schmitz, 2007). However, the

Our investigation of DHP compounds showed that many of them are capable of protecting mitochondrial processes (Fernandes et al., 2003, 2005, 2008, 2009). For instance, the most

(Sengupta et al., 2011), are currently used to treat Parkinson's disease.

mechanism of the antiparkinsonian action of DHPs is not yet understood.

**1. Introduction** 

**1,4-Dihydropyridine Compounds** 

Egils Bisenieks5, Brigita Vigante5 and Vija Klusa1

*4CNC, Faculty of Medicine, University of Coimbra, Coimbra 5Laboratory of Membrane Active and beta-Diketone Compounds,* 

**Adamantane-Containing** 

*Latvian Institute of Organic Synthesis, Riga* 

Aflatoxin exposure and risk of hepatocellular carcinoma in Taiwan. *International Journal Cancer*. Vol.67, No.5, pp.620-625.

