Análisis del sistema endocannabinoide en la enfermedad de parkinsonhacia un tratamiento polivalente

  1. Palomo Garo, Cristina
Supervised by:
  1. Javier Fernández Ruiz Director
  2. M. Concepción García García Co-director

Defence university: Universidad Complutense de Madrid

Fecha de defensa: 08 November 2016

Committee:
  1. José Antonio Ramos Atance Chair
  2. Onintza Sagredo Secretary
  3. Julián Romero Paredes Committee member
  4. Rosario Moratalla Villalba Committee member
  5. José A. Martínez Orgado Committee member
Department:
  1. Bioquímica y Biología Molecular

Type: Thesis

Abstract

Parkinson's disease (PD) is the second most common chronic neurodegenerative disease after Alzheimer's disease and its most characteristic symptoms are tremor, slowness to perform movements, rigidity and postural instability. Symptoms of PD are caused by a progressive loss of dopaminergic neurons located in the substantia nigra pars compacta which decreases dopamine levels in the striatum. At the present time, the only therapy is dopamine replacement, which causes effectiveness and a long-term side effect called dyskinesia. So far, the existing treatments are aimed at relieving symptoms but has not yet found a remedy to the neuronal death. The endocannabinoid system includes the endogenous cannabinoids and their synthetic and degradative enzymes. It is involved in multiple signaling pathways and has been postulated as a target for the treatment of PD due to the changes experienced during the course of this and other neurodegenerative diseases and its regulatory role in inflammation that occurs in these diseases. In research, it is necessary to identify the changes that the endocannabinoid system exhibits during the course of the PD, in order to find new biomarkers and new therapeutic targets and treatments aimed at developing new drugs, not only for alleviation of the symptoms, but for delay neuronal death. So, one of the strategies in the therapy of PD would be to find cannabinoid molecules that have ability to control inflammatory events, primarily through activation of cannabinoid receptor CB2 or the PPAR nuclear receptors family, providing neuroprotection and alleviating specific symptoms such as bradykinesia by blocking CB1 receptors. It would be also interesting a cannabinoid with an antioxidant profile and ability to decrease oxidative damage. Even these molecules could be combined with less pro-dyskinetic doses of L-DOPA , preserving its therapeutic effect and decreasing the side effects risk...