Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences Kraków, Poland.
Front Cell Neurosci. 2015 Mar 6;9:56. doi: 10.3389/fncel.2015.00056. eCollection 2015.
Neurodegenerative diseases are one of the main causes of mental and physical disabilities. Neurodegeneration has been estimated to begin many years before the first clinical symptoms manifest, and even a prompt diagnosis at this stage provides very little advantage for a more effective treatment as the currently available pharmacotherapies are based on disease symptomatology. The etiology of the majority of neurodegenerative diseases remains unknown, and even for those diseases caused by identified genetic mutations, the direct pathways from gene alteration to final cell death have not yet been fully elucidated. Advancements in genetic engineering have provided many transgenic mice that are used as an alternative to pharmacological models of neurodegenerative diseases. Surprisingly, even the models reiterating the same causative mutations do not fully recapitulate the inevitable neuronal loss, and some fail to even show phenotypic alterations, which suggests the possible existence of compensatory mechanisms. A better evaluation of these mechanisms may not only help us to explain why neurodegenerative diseases are mostly late-onset disorders in humans but may also provide new markers and targets for novel strategies designed to extend neuronal function and survival. The aim of this mini-review is to draw attention to this under-explored field in which investigations may reasonably contribute to unveiling hidden reserves in the organism.
神经退行性疾病是导致精神和身体残疾的主要原因之一。神经退行性变据估计早在出现第一个临床症状前多年就已开始，而即使在这个阶段及时诊断，也几乎无法提供更有效的治疗优势，因为目前可用的药物治疗是基于疾病的症状学。大多数神经退行性疾病的病因仍不清楚，即使对于那些由已确定的基因突变引起的疾病，从基因改变到最终细胞死亡的直接途径也尚未完全阐明。基因工程的进步提供了许多转基因小鼠，它们被用作神经退行性疾病的药理学模型的替代物。令人惊讶的是，即使是重复相同致病突变的模型也不能完全重现不可避免的神经元丧失，有些甚至未能显示表型改变，这表明可能存在代偿机制。对这些机制的更好评估不仅可以帮助我们解释为什么神经退行性疾病在人类中大多是迟发性疾病，还可以为旨在延长神经元功能和存活的新策略提供新的标志物和靶点。本综述的目的是提请人们注意这一尚未充分探索的领域，在这一领域的研究可能有助于揭示机体的潜在储备。
