Title:Aminochrome as New Preclinical Model to Find New Pharmacological Treatment that Stop the Development of Parkinson’s Disease
Volume: 23
Issue: 4
Author(s): Juan Segura-Aguilar, Patricia Muñoz and Irmgard Paris
Affiliation:
关键词:
多巴胺，药物代谢，醌，氨基铬，M2-2谷胱甘肽转移酶，心肌黄酶，帕金森病，神经退行性疾病
摘要: The pharmacological treatment of Parkinson´s disease (PD) is limited to dopamine
agonists and anti-cholinergic drugs that do not stop the progress of disease. LDopa
was introduced to the treatment in 1967; this drug is still the best and most commonly
used drug since it generates a real improvement in patient quality of life, but the disadvantage
of L-dopa is that this positive effect is followed by severe side effects such as
dyskinesia. The search for a new drug in the treatment of PD is limited to compounds which decrease the
side effects of the drugs used in the treatment of the disease, such as L-dopa-induced dyskinesia. One possible
explanation for pharmaceutical companies not developing new drugs to stop disease development is
because the mechanism which induces the loss of dopaminergic neurons containing neuromelanin of
the nigrostriatal system is still unknown. The discovery of genes (alpha-synuclein, parkin, pink-1, DJ-
1, LRRK2, GBA1, etc.) associated with familial forms of PD resulted in an enormous input into basic research
in order to understand the role of these proteins in the disease. It is generally accepted that the loss
of dopaminergic neurons containing neuromelanin involves mitochondrial dysfunction, protein degradation
dysfunction, the aggregation of alpha-synuclein to neurotoxic oligomers, oxidative neuroinflammation
and endoplasmic reticulum stress, but the question of what induces these mechanisms remains unanswered.
Aminochrome, the product of dopamine oxidation and the precursor of neuromelanin, is directly involved
in five of the six mechanisms and may be a better PD preclinical model.
