Abstract
BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disorder. In addition to its highly debilitating motor symptoms, non-motor symptoms may precede their motor counterparts by many years, which may characterize a prodromal phase of PD. A potential pharmacological strategy is to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death. N-acetylcysteine (NAC) has been used against paracetamol overdose hepatotoxicity by restoring hepatic concentrations of glutathione (GSH), and as a mucolytic in chronic obstructive pulmonary disease by reducing disulfide bonds in mucoproteins. It has been shown to be safe for humans at high doses. More recently, several studies have evidenced that NAC has a multifaceted mechanism of action, presenting indirect antioxidant effect by acting as a GSH precursor, besides its anti-inflammatory and neurotrophic effects. Moreover, NAC modulates glutamate release through activation of the cystine-glutamate antiporter in extra-synaptic astrocytes. Its therapeutic benefits have been demonstrated in clinical trials for several neuropsychiatric conditions but has not been tested in PD models yet.MethodsIn this study, we evaluated the potential of NAC to prevent the damage induced by 6-hydroxydopamine (6-OHDA) on motor, optomotor and morphological parameters in a PD model in larval zebrafish.ResultsNAC was able to prevent the motor deficits (total distance, mean speed, maximum acceleration, absolute turn angle and immobility time), optomotor response impairment and morphological alterations (total length and head length) caused by exposure to 6-OHDA, which reinforce and broaden the relevance of its neuroprotective effects.DiscussionNAC acts in different targets relevant to PD pathophysiology. Further studies and clinical trials are needed to assess this agent as a candidate for prevention and adjunctive treatment of PD.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the world, affecting on average 2–3% of the individuals older than 65 years (Poewe et al, 2017)
We evaluated the potential of NAC to prevent the injury caused by 6-OHDA exposure on motor, optomotor response and morphological parameters in zebrafish larvae
Larvae exposed to 6-OHDA spent less time in the stimulus zone, and NAC was able to prevent this optomotor deficit
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the world, affecting on average 2–3% of the individuals older than 65 years (Poewe et al, 2017) This condition originates from progressive death of dopamine (DA) neurons in the substantia nigra pars compacta of the midbrain and is characterized by motor and non-motor symptoms (Kalia & Lang, 2015). A potential pharmacological strategy would be to identify individuals in the prodromal phase and to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death (Dexter & Jenner, 2013). Methods: In this study, we evaluated the potential of NAC to prevent the damage induced by 6-hydroxydopamine (6-OHDA) on motor, optomotor and morphological parameters in a PD model in larval zebrafish.
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