Title:Cysteine Network (CYSTEINET) Dysregulation in Parkinson’s Disease: Role of N-acetylcysteine
VOLUME: 17 ISSUE: 4
Author(s):Marcos Martínez-Banaclocha
Affiliation:Department of Pathology, Hospital Lluis Alcanyis, Xátiva, Spain.
Keywords:Acetylcysteine, cysteine, cysteinet, neurodegeneration, Parkinson, reactive species, redox homeostasis, thiol.
Abstract:Background: Reactive species have been regarded as by-products of cellular metabolism, which cause oxidative damage contributing
to aging and neurodegenerative diseases. However, accumulated evidence support the notion that reactive species mediate intracellular
and extracellular signals that regulate physiological functions including posttranslational protein modifications. Cysteine thiol groups of
proteins are particularly susceptible to oxidative modifications by oxygen, nitrogen and sulfur species generating different products with
critical roles in the cellular redox homeostasis. At physiological conditions, reactive species can function not only as intracellular second
messengers with regulatory roles in many cellular metabolic processes but also as part of an ancestral biochemical network that controls
cellular survival, regeneration, and death.
Objective: To propose a biochemical network, called cellular cysteine network (CYSTEINET), which can be dysregulated in Parkinson’s
disease. Due to the fact that there are many cysteine-bearing proteins and cysteine-dependent enzymes susceptible to oxidative modifications,
it is proposed that oxidative-changed proteins at cysteine residues may be critical for Parkinson’s disease development.
Conclusion: In the present review, I advance the concept that “cysteinet” is impaired in Parkinson’s disease resulting in a functional and
structural dysregulation of the matrix of interconnected cysteine-bearing proteins, which in conjunction with reactive species and glutathione
regulate the cellular bioenergetic metabolism, the redox homeostasis, and the cellular survival. This network may represent an
ancestral down-top system composed of a complex matrix of proteins with very different cellular functions, but bearing the same regulatory
thiol radical. Finally, the possible role of N-acetylcysteine and derivatives to regulate “cysteinet” and slow down Parkinson’s disease
development and progression is discussed.
