Panegyres Peter K
Neurodegenerative Disorders Research Pty Ltd., Perth 6005, Australia.
School of Medicine, The University of Western Australia, Perth 6009, Australia.
Brain Sci. 2022 Feb 7;12(2):226. doi: 10.3390/brainsci12020226.
We previously suggested that stochastic processes are fundamental in the development of sporadic adult onset neurodegenerative disorders. In this study, we develop a theoretical framework to explain stochastic processes at the protein, DNA and RNA levels. We propose that probability determines random sequencing changes, some of which favor neurodegeneration in particular anatomical spaces, and that more than one protein may be affected simultaneously. The stochastic protein changes happen in three-dimensional space and can be considered to be vectors in a space-time continuum, their trajectories and kinetics modified by physiological variables in the manifold of intra- and extra-cellular space. The molecular velocity of these degenerative proteins must obey the second law of thermodynamics, in which entropy is the driver of the inexorable progression of neurodegeneration in the context of the N-body problem of interacting proteins, time-space manifold of protein-protein interactions in phase space, and compounded by the intrinsic disorder of protein-protein networks. This model helps to elucidate the existence of multiple misfolded proteinopathies in adult sporadic neurodegenerative disorders.
我们之前曾提出，随机过程在散发性成人神经退行性疾病的发展中起着基础性作用。在本研究中，我们构建了一个理论框架来解释蛋白质、DNA和RNA水平上的随机过程。我们提出，概率决定随机的序列变化，其中一些变化尤其有利于特定解剖区域的神经退行性变，并且可能同时影响不止一种蛋白质。随机的蛋白质变化发生在三维空间中，可以被视为时空连续统中的向量，其轨迹和动力学受到细胞内和细胞外空间流形中生理变量的影响。这些退行性蛋白质的分子速度必须遵循热力学第二定律，在相互作用蛋白质的N体问题、相空间中蛋白质-蛋白质相互作用的时空流形以及蛋白质-蛋白质网络的内在无序性的背景下，熵是神经退行性变不可阻挡进展的驱动因素。该模型有助于阐明成人散发性神经退行性疾病中多种错误折叠蛋白病的存在。
