Panegyres Peter K
Neurodegenerative Disorders Research Pty Ltd., Perth, WA 6005, Australia; Tel.: +61-8-6317-9472.
School of Medicine, The University of Western Australia, Perth, WA 6009, Australia.
Brain Sci. 2025 Jul 29;15(8):814. doi: 10.3390/brainsci15080814.
The mechanisms by which sporadic young-onset neurodegenerative processes develop are uncertain.
We have previously proposed that stochastic processes involving sequence changes at a DNA, RNA, or protein level in critical genes and proteins might be important to this process. Further investigation points to the contribution of probabilistic states in other factors involved in neurodegenerative conditions, such as-in the case of young onset Alzheimer's disease-head injury, apolipoprotein ε4 alleles and other elements that, by the interaction of conditional probabilities in these variables, influence the evolution of neurodegenerative conditions.
This proposal might help to explain why some autosomal dominant neurodegenerative conditions, such as trinucleotide repeat disorder (Huntington's disease), might have variable ages of onset given the same disease-causing CAG repeat mutation length.
The detection of somatic mutations in single brain cells provides some experimental support for these emerging concepts.
散发性早发性神经退行性病变发展的机制尚不确定。
我们之前曾提出，涉及关键基因和蛋白质在DNA、RNA或蛋白质水平上序列变化的随机过程可能对这一过程很重要。进一步研究表明，神经退行性疾病所涉及的其他因素中的概率状态也有作用，例如在早发性阿尔茨海默病中，头部损伤、载脂蛋白ε4等位基因以及其他因素，通过这些变量中条件概率的相互作用，影响神经退行性疾病的发展。
这一观点可能有助于解释为什么某些常染色体显性神经退行性疾病，如三核苷酸重复紊乱（亨廷顿舞蹈病），在致病CAG重复突变长度相同时，发病年龄却有所不同。
在单个脑细胞中检测体细胞突变，为这些新出现的概念提供了一些实验支持。
