R-loop Mediated DNA Damage and Impaired DNA Repair in Spinal Muscular Atrophy.
R-loop Mediated DNA Damage and Impaired DNA Repair in Spinal Muscular Atrophy.
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DOI：
10.3389/fncel.2022.826608
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发表时间：
2022
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
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作者：
DNA修复途径的缺陷是DNA损伤积累导致基因组不稳定和神经变性的主要原因。有效的DNA损伤修复是维持基因组稳定性、支持细胞功能和活力的关键。DNA损伤导致细胞死亡通路的激活，导致越来越多的神经疾病的神经元死亡，如肌萎缩侧索硬化症(ALS)、帕金森病(PD)、阿尔茨海默病(AD)和脊髓性肌萎缩症(SMA)。SMA是一种由存活运动神经元1(SMN1)基因突变引起的神经退行性疾病。SMA的特点是脊髓运动神经元由于低水平的SMN蛋白而变性。近20年来，SMA选择性运动神经元变性的分子机制一直不清楚。然而，一些研究已经确定了可能导致SMA运动神经元主要变性的生化和分子机制，包括RhoA/ROCK、c-Jun NH2末端激酶(JNK)和P53介导的通路，这些通路参与了DNA损伤依赖的细胞死亡。最近的研究为运动神经元的选择性变性提供了新的视角，这可能是由于R环介导的DNA损伤和非同源末端连接(NHEJ)DNA修复途径的损害导致基因组不稳定所致。在这里，我们回顾了关于R-环介导的DNA损伤和SMA中神经元特异性DNA修复机制缺陷的最新发现，并在与DNA损伤相关的其他神经退行性疾病的背景下讨论这些发现。
Defects in DNA repair pathways are a major cause of DNA damage accumulation leading to genomic instability and neurodegeneration. Efficient DNA damage repair is critical to maintain genomicstability and support cell function and viability. DNA damage results in the activation of cell death pathways, causing neuronal death in an expanding spectrum of neurological disorders, such as amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), Alzheimer’s disease (AD), and spinal muscular atrophy (SMA). SMA is a neurodegenerative disorder caused by mutations in the Survival Motor Neuron 1 (SMN1) gene. SMA is characterized by the degeneration of spinal cord motor neurons due to low levels of the SMN protein. The molecular mechanism of selective motor neuron degeneration in SMA was unclear for about 20 years. However, several studies have identified biochemical and molecular mechanisms that may contribute to the predominant degeneration of motor neurons in SMA, including the RhoA/ROCK, the c-Jun NH2-terminal kinase (JNK), and p53-mediated pathways, which are involved in mediating DNA damage-dependent cell death. Recent studies provided insight into selective degeneration of motor neurons, which might be caused by accumulation of R-loop-mediated DNA damage and impaired non-homologous end joining (NHEJ) DNA repair pathway leading to genomic instability. Here, we review the latest findings involving R-loop-mediated DNA damage and defects in neuron-specific DNA repair mechanisms in SMA and discuss these findings in the context of other neurodegenerative disorders linked to DNA damage.
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影响因子：
3.5
作者：
Bhatia V;Herrera-Moyano E;Aguilera A;Gómez-González B
通讯作者：
Gómez-González B
影响因子：
--
作者：
Ahmad S;Bhatia K;Kannan A;Gangwani L
通讯作者：
Gangwani L
影响因子：
5.5
作者：
Cheng C;Seen D;Zheng C;Zeng R;Li E
通讯作者：
Li E
影响因子：
64.8
作者：
Aktas, Tugce;Ilik, Ibrahim Avsar;Akhtar, Asifa
通讯作者：
Akhtar, Asifa
DOI：
10.1007/978-3-319-89689-2_10
发表时间：
2018-01-01
期刊：
RNA METABOLISM IN NEURODEGENERATIVE DISEASES
影响因子：
--
作者：
Bennett, Craig L.;La Spada, Albert R.
通讯作者：
La Spada, Albert R.