Energy metabolism and Protein synthesis in Parkinson's disease and Dementia with Lewy Bodies

Author

Anusha, Koneti

Director

Ferrer, Isidro (Ferrer Abizanda)

Date of defense

2015-10-02

Pages

189 p.



Department/Institute

Universitat de Barcelona. Facultat de Medicina

Abstract

Mitochondria dysfunction is documented in the substantia nigra in Parkinson's disease (PD), a region which plays a central role in the characteristic motor manifestations of the disease. Mitochondria! dysfunction is a cause of neuron energy exhaustion, oxidative stress and dopaminergic cell death. However, little is known about mitochondria! dysfunction in other brain regions in PD, the impairment of which is causative of other symptoms such as cognitive impairment and, in some cases, dementia. The present study was undertaken to analyse mitochondria! function in the frontal cortex area 8 and angular gyrus. On the other hand, protein synthesis has also been shown to play role in neurodegenerative diseases which leads to neuronal atrophy. It is reported that significant percentage of protein synthesis results in the generation of defective ribosomal products, occurring as the result of faulty coding/or transfer within the ribosomal complex. The present study was undertaken to analyse impairment of ribosomal subunits in substantia nigra, frontal cortex area 8, angular gyrus, and precuneus. The frozen human post-mortem brain samples obtained following generous donation after informed consent, and stored at the Institute of Neuropathology Brain Bank (a branch of the HUB-ICO-IDIBELL brain bank). The study contemplates different stages of disease progression, according to the findings of the neuropathological study, and includes expression levels of mRNA and protein of selected subunits of the mitochondria! complexes and ribosomal subunits, and also enzymatic activities of each one of these complexes compared to those seen in age-matched controls processed in parallel. Results show altered activity of selected complexes of the respiratory chain thus supporting the concept that mitochondria! alterations in PD are not restricted to the substantia nigra but they rather represent a more widespread region-dependent alteration in PD. On the other hand the results of ribosomal proteins show disease-dependent differences in ribosomal protein gene expression.

Keywords

Mitocondris; Mitocondrias; Mitochondria; Malaltia de Parkinson; Enfermedad de Parkinson; Parkinson's disease; Demència amb cossos de Lewy; Demencia de cuerpos de Lewy; Lewy body dementia

Subjects

616.8 - Neurology. Neuropathology. Nervous system

Knowledge Area

Ciències de la Salut

Documents

Koneti_Anusha_THESIS.pdf

8.632Mb

 

Rights

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