Institute for Glycomics, Gold Coast Campus, Griffith University, Southport, QLD 4222, Australia.
School of Pharmacy and Medical Science, Gold Coast Campus, Griffith University, Southport, QLD 4222, Australia.
Cells. 2022 Dec 6;11(23):3938. doi: 10.3390/cells11233938.
The variety of drugs available to treat neurodegenerative diseases is limited. Most of these drug's efficacy is restricted by individual genetics and disease stages and usually do not prevent neurodegeneration acting long after irreversible damage has already occurred. Thus, drugs targeting the molecular mechanisms underlying subsequent neurodegeneration have the potential to negate symptom manifestation and subsequent neurodegeneration. Neuroinflammation is a common feature of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis, and is associated with the activation of the NLRP3 inflammasome, which in turn leads to neurodegeneration. Inflammasome activation and oligomerisation is suggested to be a major driver of disease progression occurring in microglia. With several natural products and natural product derivatives currently in clinical trials, mushrooms have been highlighted as a rich and largely untapped source of biologically active compounds in both in vitro and in vivo neurodegenerative disease models, partially supported by successful clinical trial evaluations. Additionally, novel high-throughput methods for the screening of natural product compound libraries are being developed to help accelerate the neurodegenerative disease drug discovery process, targeting neuroinflammation. However, the breadth of research relating to mushroom natural product high-throughput screening is limited, providing an exciting opportunity for further detailed investigations.
用于治疗神经退行性疾病的药物种类有限。这些药物的大多数疗效受到个体遗传学和疾病阶段的限制，通常不能预防在已经发生不可逆转损伤之后发生的神经退行性变。因此，针对后续神经退行性变的分子机制的药物具有消除症状表现和随后的神经退行性变的潜力。神经炎症是阿尔茨海默病、帕金森病、亨廷顿病和多发性硬化症等神经退行性疾病的共同特征，与 NLRP3 炎性小体的激活有关，而 NLRP3 炎性小体又会导致神经退行性变。炎性小体的激活和寡聚化被认为是小胶质细胞中发生疾病进展的主要驱动因素。由于目前有几种天然产物和天然产物衍生物正在进行临床试验，蘑菇已被强调为具有生物活性化合物的丰富且在很大程度上未开发的来源，这在一定程度上得到了成功的临床试验评估的支持。此外，正在开发用于筛选天然产物化合物库的新型高通量方法，以帮助加速针对神经炎症的神经退行性疾病药物发现过程。然而，与蘑菇天然产物高通量筛选相关的研究范围有限，为进一步的详细研究提供了令人兴奋的机会。
