High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease

By A. Bender, K. J. Krishnan, C. Morris, G. Taylor, A. Reeve, R. Perry, E. Jaros, J. Hersheson, J. Betts, T. Klopstock and 2 more. Nature Genetics, 2006

1,528 citations recorded by the source corpus.

Subfields: Cellular and Molecular Neuroscience, Clinical Biochemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f9c21287c66a927c184c235b9ba6e9427d923303

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. D. C. Chan
2. A. Johri
3. M. Mouradian
4. V. Dias
5. E. Junn
6. S. Gandhi
7. M. Beal
8. A. Abramov

In Clinical Biochemistry

1. D. C. Chan
2. Hsiuchen Chen
3. R. Youle
4. J. Nunnari
5. Xiongwei Zhu
6. Xinglong Wang
7. M. Beal
8. A. Johri

In Molecular Biology

1. D. C. Chan
2. R. Youle
3. Hsiuchen Chen
4. J. Nunnari
5. A. Suomalainen
6. Xiongwei Zhu
7. Xinglong Wang
8. A. Johri

Citations in the corpus

• Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease (2012, background): “Indeed, high levels of somatic mtDNA mutations have been observed in substantia nigra neurons with OXPHOS enzyme defects in aged human and PD patients [112,113], suggesting that somatic mtDNA deletions are important in the selective neuronal loss observed in brain aging and in PD.”
• Mitochondrial Dysfunction in Parkinson's Disease (2011, background): “Moreover, mutations in several mitochondrial proteins have been associated with familial forms of PD [5–7], as well as the presence of deletions in mitochondrial DNA identified in aging controls and PD substantia nigra [8].”
• Role of Oxidative Stress in Parkinson's Disease (2013, background): “Higher numbers of respiratory chain deficient DA neurons have been found in PD patients than in age-matched controls [27].”
• Mitochondria: In Sickness and in Health (2012, background): “Data from cell culture models suggest the intriguing possibility that defective mitochondrial quality control contributes more generally to Parkinson-like phenotypes, potentially explaining why mtDNA mutation accumulate in substantia nigra neurons (Bender et al., 2006; Kraytsberg et al., 2006).”
• The Role of Oxidative Stress in Parkinson’s Disease (2013, background): “In aged and PD afflicted brains, high levels of mitochondrial DNA (mtDNA) deletions are found in pigmented neurons of the substantia nigra [192] [193] [194] [195], and ROS-mediated damage can result in mutations in the mitochondrial genome [196] [197] [198].”
• Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences (2012, positive): “An age-dependent increase in mtDNA deletions has been found in individual DA neurons dissected from the SNc of post mortem human brain (Bender et al , 2006; Kraytsberg et al , 2006).”
• The Roles of PINK1, Parkin and Mitochondrial Fidelity in Parkinson's Disease (2015, background): “SN neurons from autopsies of normal-aged people and PD patients harbor high levels of mutated mtDNA with largescale deletions that cause mitochondrial dysfunction (Bender et al., 2006; Kraytsberg et al., 2006).”
• Mitochondrial dysfunction: mechanisms and advances in therapy (2024, background): “228,247 The aggregation of alpha-synuclein ( α -Syn), a de fi ning feature of PD ’ s neuropathology through Lewy body formation, further compounds these mitochondrial challenges.”
• DNA damage and its links to neurodegeneration (2014, positive): “Similarly, elevated levels of oxidative lesions and SSBs have been reported in the neurons of ALS patients and damage to mitochondrial DNA has been documented in PD (Bender et al., 2006; Kraytsberg et al., 2006; Martin, 2001).”
• Metals, oxidative stress and neurodegenerative disorders (2010, neutral): “mitochondria-associated metabolic proteins [106–108].”
• Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations (2010, positive): “…work, it will be important to address whether mitochondrial fusion plays an analogous protective role against age-associated mtDNA deletions, which similarly cause cellular dysfunction only upon clonal expansion to high levels (Bender et al., 2006; Kraytsberg et al., 2006; Wanagat et al., 2001).”