Cheslow Lara, Snook Adam E, Waldman Scott A
Department of Pharmacology, Physiology and Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Department of Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Biomolecules. 2024 Mar 26;14(4):398. doi: 10.3390/biom14040398.
Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD).
神经系统疾病是全球认知和身体残疾的主要原因,影响着全球15%的人口。由于人口老龄化,包括神经退行性疾病在内的神经系统疾病的患病率在未来二十年内将翻一番。不幸的是,尽管现有疗法能为认知和运动障碍提供症状缓解,但迫切需要开发能减缓病理进展速度的疾病修饰疗法。在这种情况下,生物标志物可以识别有风险和前驱期的患者,监测疾病进展,追踪治疗反应,并剖析分子事件的因果关系以识别新的进一步临床研究靶点。因此,识别能区分疾病并反映病理特定阶段的生物标志物将推动治疗靶点的发现和开发。本综述将描述三种最常见的神经退行性疾病,包括阿尔茨海默病(AD)、肌萎缩侧索硬化症(ALS)和帕金森病(PD)的患病率、已知机制、正在进行或最近结束的治疗性临床试验以及生物标志物。