Martinez-Banaclocha Marcos
Department of Pathology, Lluis Alcanyis Hospital, Xátiva, 46800 Valencia, Spain.
Antioxidants (Basel). 2022 Feb 18;11(2):416. doi: 10.3390/antiox11020416.
In the last twenty years, significant progress in understanding the pathophysiology of age-associated neurodegenerative diseases has been made. However, the prevention and treatment of these diseases remain without clinically significant therapeutic advancement. While we still hope for some potential genetic therapeutic approaches, the current reality is far from substantial progress. With this state of the issue, emphasis should be placed on early diagnosis and prompt intervention in patients with increased risk of neurodegenerative diseases to slow down their progression, poor prognosis, and decreasing quality of life. Accordingly, it is urgent to implement interventions addressing the psychosocial and biochemical disturbances we know are central in managing the evolution of these disorders. Genomic and proteomic studies have shown the high molecular intricacy in neurodegenerative diseases, involving a broad spectrum of cellular pathways underlying disease progression. Recent investigations indicate that the dysregulation of the sensitive-cysteine proteome may be a concurrent pathogenic mechanism contributing to the pathophysiology of major neurodegenerative diseases, opening new therapeutic opportunities. Considering the incidence and prevalence of these disorders and their already significant burden in Western societies, they will become a real pandemic in the following decades. Therefore, we propose large-scale investigations, in selected groups of people over 40 years of age with decreased blood glutathione levels, comorbidities, and/or mild cognitive impairment, to evaluate supplementation of the diet with low doses of -acetyl-cysteine, a promising and well-tolerated therapeutic agent suitable for long-term use.
在过去二十年里，我们对年龄相关性神经退行性疾病的病理生理学的理解取得了重大进展。然而，这些疾病的预防和治疗在临床上仍未取得显著的治疗进展。虽然我们仍寄希望于一些潜在的基因治疗方法，但目前的现实距离实质性进展还很远。鉴于此问题的现状，应重点关注对神经退行性疾病风险增加的患者进行早期诊断和及时干预，以减缓其疾病进展、不良预后以及生活质量下降。因此，迫切需要实施干预措施，解决我们已知在管理这些疾病演变过程中至关重要的心理社会和生化紊乱问题。基因组和蛋白质组学研究表明，神经退行性疾病存在高度的分子复杂性，涉及疾病进展背后的广泛细胞通路。最近的研究表明，敏感半胱氨酸蛋白质组的失调可能是导致主要神经退行性疾病病理生理学的一种并发致病机制，从而带来了新的治疗机会。考虑到这些疾病的发病率和患病率以及它们在西方社会已经造成的巨大负担，在接下来的几十年里，它们将成为一场真正的大流行疾病。因此，我们建议对40岁以上、血液谷胱甘肽水平降低、患有合并症和/或轻度认知障碍的特定人群组进行大规模调查，以评估用低剂量的N - 乙酰半胱氨酸补充饮食的效果，N - 乙酰半胱氨酸是一种有前景且耐受性良好、适合长期使用的治疗药物。
