The degeneration and replacement of dopamine cells in Parkinson’s disease: the role of aging

Abstract

Available data show marked similarities for the degeneration of dopamine cells in Parkinson’s disease (PD) and aging. The etio-pathogenic agents involved are very similar in both cases, and include free radicals, different mitochondrial disturbances, alterations of the mitophagy and the ubiquitin-proteasome system. Proteins involved in PD such as α-synuclein, UCH-L1, PINK1 or DJ-1, are also involved in aging. The anomalous behavior of astrocytes, microglia and stem cells of the subventricular zone (SVZ) also changes similarly in aging brains and PD. Present data suggest that PD could be the expression of aging on a cell population with high vulnerability to aging. The future knowledge of mechanisms involved in aging could be critical for both understanding the etiology of PD and developing etiologic treatments to prevent the onset of this neurodegenerative illness and to control its progression.

Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative diseases: An aging effect

“…The subsequent oxidative stress will then facilitate the aggregation of α-synuclein (Takahashi et al, 2007). Aggregation of α-synuclein forms Lewy bodies and Lowy neurites, both of which are hallmarks of PD (Rodriguez et al, 2016; Rodriguez et al, 2015). …”

“…Dopaminergic neurons are equipped with unmyelinated axons, and thus astrocytes make the most intimate contact with them (Rodriguez et al, 2016). Intact astrocytes provide protection and support to dopaminergic neurons through producing antioxidants such as glutathione, and through removing toxic molecules including glutamate and α-synuclein (Rappold and Tieu, 2010).…”

A WNT1-regulated developmental gene cascade prevents dopaminergic neurodegeneration in adult En1 mice

“…Aging is the largest risk factor in PD (Rodriguez et al, 2014), suggesting that the loss of mdDA neurons in PD and genetic animal models such as the En1 +/− mice is initially (at younger ages) alleviated by neuroprotective mechanisms. Moreover, mdDA neuron numbers and striatal innervation as well as DA release show a remarkable ability to recover after acute or chronic administration of MPTP or 6-OHDA in young but not aged animals (Blandini and Armentero, 2012;Bove and Perier, 2012).…”

Efeito dos Antioxidantes Exógenos em Modelos Experimentais da Doença de Parkinson

“…A DP é um transtorno neurodegenerativo progressivo e irreversível, de origem predominantemente idiopática, caracterizado pela morte de neurônios dopaminérgicos na pars compacta da substância nigra, uma região do cérebro que controla a atividade motora e projeta axônios dopaminérgicos para o estriado (TERAO et al, 2013). A diminuição de dopamina nos núcleos da base induz uma redução da ativação do tálamo, o que resulta em uma inibição excessiva das respostas motoras, levando aos sinais clínicos da DP, principalmente relacionados à motricidade, que incluem tremores, rigidez, bradicinesia, hipocinesia e dificuldades para cami-nhar (RODRIGUEZ et al, 2014). Em estágios mais avançados, a perda de dopamina acaba por acometer também outras regiões do córtex cerebral, do tronco e da medula espinhal, levando o paciente a desenvolver sinais não motores, tais como distúrbios do sono e disfunção cognitiva, incluindo a demência (DE JESUS-CORTÉS et al, 2012 (MATTSON, 2006;PERIER et al, 2007).…”