SDG 03 Group - Good Health & Well-being, Landmark University, Omu-Aran 251101, Kwara State, Nigeria.
Department of Biochemistry, Medicinal Biochemistry, Nanomedicine & Toxicology Laboratory, Landmark University, PMB 1001, Omu-Aran-251101, Nigeria.
Oxid Med Cell Longev. 2021 Nov 10;2021:5522981. doi: 10.1155/2021/5522981. eCollection 2021.
Neurodegenerative diseases (NDs) like Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease predominantly pose a significant socioeconomic burden. Characterized by progressive neural dysfunction coupled with motor or intellectual impairment, the pathogenesis of ND may result from contributions of certain environmental and molecular factors. One such condition is hypoxia, characterized by reduced organ/tissue exposure to oxygen. Reduced oxygen supply often occurs during the pathogenesis of ND and the aging process. Despite the well-established relationship between these two conditions (i.e., hypoxia and ND), the underlying molecular events or mechanisms connecting hypoxia to ND remain ill-defined. However, the relatedness may stem from the protective or deleterious effects of the transcription factor, hypoxia-inducible factor 1-alpha (HIF-1). The upregulation of HIF-1 occurs in the pathogenesis of most NDs. The dual function of HIF-1 in acting as a "killer factor" or a "protective factor" depends on the prevailing local cellular condition. The kynurenine pathway is a metabolic pathway involved in the oxidative breakdown of tryptophan. It is essential in neurotransmission and immune function and, like hypoxia, associated with ND. Thus, a good understanding of factors, including hypoxia (i.e., the biochemical implication of HIF-1) and kynurenine pathway activation in NDs, focusing on Alzheimer's disease could prove beneficial to new therapeutic approaches for this disease, thus the aim of this review.
神经退行性疾病（NDs），如阿尔茨海默病、多发性硬化症、肌萎缩侧索硬化症、帕金森病和亨廷顿病，主要造成重大的社会经济负担。这些疾病的特征是进行性神经功能障碍，伴有运动或智力障碍，其发病机制可能是某些环境和分子因素共同作用的结果。其中一种情况是缺氧，其特征是器官/组织供氧减少。在 ND 的发病机制和衰老过程中，通常会出现供氧减少。尽管缺氧和 ND 之间存在明确的关系，但将缺氧与 ND 联系起来的潜在分子事件或机制仍未得到明确界定。然而，这种相关性可能源于转录因子缺氧诱导因子 1-α（HIF-1）的保护或有害作用。在大多数 NDs 的发病机制中，HIF-1 的上调发生。HIF-1 的双重功能是作为“杀伤因子”或“保护因子”，这取决于当地细胞的普遍状况。犬尿氨酸途径是一种涉及色氨酸氧化分解的代谢途径。它在神经传递和免疫功能中至关重要，并且与缺氧一样，与 ND 相关。因此，深入了解包括缺氧（即 HIF-1 的生化意义）和犬尿氨酸途径激活在内的因素，关注阿尔茨海默病，可能对这种疾病的新治疗方法有益，这也是本综述的目的。
