Alu elements are a highly successful family of primate-specific retrotransposons that have fundamentally shaped primate evolution, including the evolution of our own species. Alus play critical roles in the formation of neurological networks and the epigenetic regulation of biochemical processes throughout the central nervous system (CNS), and thus are hypothesized to have contributed to the origin of human cognition. Despite the benefits that Alus provide, deleterious Alu activity is associated with a number of neurological and neurodegenerative disorders. In particular, neurological networks are potentially vulnerable to the epigenetic dysregulation of Alu elements operating across the suite of nuclear-encoded mitochondrial genes that are critical for both mitochondrial and CNS function. Here, we highlight the beneficial neurological aspects of Alu elements as well as their potential to cause disease by disrupting key cellular processes across the CNS. We identify at least 37 neurological and neurodegenerative disorders wherein deleterious Alu activity has been implicated as a contributing factor for the manifestation of disease, and for many of these disorders, this activity is operating on genes that are essential for proper mitochondrial function. We conclude that the epigenetic dysregulation of Alu elements can ultimately disrupt mitochondrial homeostasis within the CNS. This mechanism is a plausible source for the incipient neuronal stress that is consistently observed across a spectrum of sporadic neurological and neurodegenerative disorders.

中文翻译：

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警告SINE：铝元素，人脑的进化以及神经系统疾病的范围。

Alu元素是非常成功的灵长类特异性逆转座子家族，已从根本上影响了灵长类动物的进化，包括我们自身物种的进化。阿鲁斯在整个中枢神经系统（CNS）的神经网络的形成和生化过程的表观遗传调控中起着至关重要的作用，因此被认为对人类认知的起源做出了贡献。尽管Alus提供了好处，但有害的Alu活性与许多神经系统疾病和神经退行性疾病有关。特别是，神经网络可能容易受到Alu元素的表观遗传失调的影响，该元素在一系列对线粒体和CNS功能均至关重要的核编码线粒体基因中起作用。这里，我们重点介绍了Alu元素的有益神经学方面，以及它们通过破坏整个CNS的关键细胞过程引起疾病的潜力。我们鉴定出至少37种神经系统疾病和神经退行性疾病，其中有害的Alu活性已被认为是疾病表现的一个促成因素，而对于许多这些疾病，这种活性作用于对正常线粒体功能必不可少的基因。我们得出结论，Alu元素的表观遗传失调最终可能破坏CNS内的线粒体稳态。这种机制是始发性神经元应激的一个合理来源，在各种各样的散发性神经系统疾病和神经退行性疾病中一直观察到这种情况。