Della Notte, Salvatore (2022) Pharmacological improvement of mitochondrial function as strategy to prevent neuronal damage in parkinson's disease. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Resource language: English
Title: Pharmacological improvement of mitochondrial function as strategy to prevent neuronal damage in parkinson's disease
Creators:
CreatorsEmail
Della Notte, Salvatoresa.dellanotte@gmail.com
Date: 5 April 2022
Number of Pages: 104
Institution: Università degli Studi di Napoli Federico II
Department: Neuroscienze e Scienze Riproduttive ed Odontostomatologiche
Dottorato: Neuroscienze
Ciclo di dottorato: 34
Coordinatore del Corso di dottorato:
nomeemail
Taglialatela, Mauriziomaurizio.taglialatela@unina.it
Tutor:
nomeemail
Scorziello, AntonellaUNSPECIFIED
Date: 5 April 2022
Number of Pages: 104
Keywords: Parkinson's Disease, Mitochondria, Neurodegeneration, Oxidative Stress, Synapses, Toxins, Genes, Cellular model, Animal model, Behavioral experiments.
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/14 - Farmacologia
Area 06 - Scienze mediche > MED/26 - Neurologia
Date Deposited: 08 Apr 2022 11:49
Last Modified: 28 Feb 2024 11:02
URI: http://www.fedoa.unina.it/id/eprint/14400

Collection description

Parkinson’s disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta causing a deficiency of dopamine in the striatum. Specific neuropathological hallmarks of disease are represented by the presence of intraneuronal protein aggregates called Lewy bodies and Lewy neurites. The exact mechanism that leads to the selective loss of dopaminergic neurons is not yet completely clear. Some of the proposed cellular mechanisms include α-synuclein accumulation, oxidative stress, alterations of mitochondrial calcium homeostasis and mitochondrial dysfunctions. The present study was adresssed to investigate the intracellular pathways affected by ornithine treatment in in vitro and in vivo models of PD with particular regards to cellular metabolism and mitochondrial function in order to identify new and selective therapeutic strategies to prevent neuronal dysfunction occurring in PD and consequently to slow down disease progression. This aspect is extremely relevant considering the key role played by mitochondria in regulating synaptic activity. Therefore, a therapeutic strategy able to promote mitochondrial function might results useful to counteract the early synaptic dysfunction and the functional and pathological changes occurring in the brain of PD-affected patients. To this aim in vitro experiments have been performed to evaluate the effect of L-Ornithine L-Aspartate (LOLA) on mitochondrial function in two cellular models of PD represented by SH-SY5Y cells treated with rotenone (ROT), an inhibitor of mitochondrial complex I, and 6-hydroxydopamine (6-OHDA), an inducer of oxidative stress. Parallel in vivo experiments have been performed in mice expressing the mutation A53T of human α-synuclein (A53T-α-Syn) during aging, to evaluate the relationship between α-synuclein accumulation, mitochondrial dysfunction and behavioral phenotype of A53T-α-Syn-mice compared to WT, with particular regard to the motor and non-motor symptoms. These experiments will allow to identify an animal model recapitulating the prodromal phase of PD potentially useful to investigate the effect of drugs able to improve mitochondria function in animal models of PD progression.

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