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Parkinson Disease: HELP
Articles by Sangwoo Ham
Based on 7 articles published since 2010
(Why 7 articles?)
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Between 2010 and 2020, Sangwoo Ham wrote the following 7 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Article Therapeutic Evaluation of Synthetic Peucedanocoumarin III in an Animal Model of Parkinson's Disease. 2019

Ham, Sangwoo / Kim, Heejeong / Yoon, Jin-Ha / Kim, Hyojung / Song, Bo Reum / Choi, Jeong-Yun / Lee, Yun-Song / Paek, Seung-Mann / Maeng, Han-Joo / Lee, Yunjong. ·Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 16419, Korea. ham89p12@skku.edu. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 16419, Korea. kimhj9301@gmail.com. · College of Pharmacy, Gachon University, Incheon 21936, Korea. jinha89@daum.net. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 16419, Korea. hjung93@skku.edu. · College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju Daero 501, Jinju 52828, Gyeongnam, Korea. qhfma2005@naver.com. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 16419, Korea. choijy@skku.edu. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 16419, Korea. yslee@skku.edu. · College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju Daero 501, Jinju 52828, Gyeongnam, Korea. million@gnu.ac.kr. · College of Pharmacy, Gachon University, Incheon 21936, Korea. hjmaeng@gachon.ac.kr. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 16419, Korea. ylee69@skku.edu. ·Int J Mol Sci · Pubmed #31689937.

ABSTRACT: The motor and nonmotor symptoms of Parkinson's disease (PD) correlate with the formation and propagation of aberrant α-synuclein aggregation. This protein accumulation is a pathological hallmark of the disease. Our group recently showed that peucedanocoumarin III (PCIII) possesses the ability to disaggregate β sheet aggregate structures, including α-synuclein fibrils. This finding suggests that PCIII could be a therapeutic lead compound in PD treatment. However, the translational value of PCIII and its safety information have never been explored in relevant animal models of PD. Therefore, we first designed and validated a sequence of chemical reactions for the large scale organic synthesis of pure PCIII in a racemic mixture. The synthetic PCIII racemate facilitated clearance of repeated β sheet aggregate (β23), and prevented β23-induced cell toxicity to a similar extent to that of purified PCIII. Given these properties, the synthetic PCIII's neuroprotective function was assessed in 6-hydroxydopamine (6-OHDA)-induced PD mouse models. The PCIII treatment (1 mg/kg/day) in a 6-OHDA-induced PD mouse model markedly suppressed Lewy-like inclusions and prevented dopaminergic neuron loss. To evaluate the safety profiles of PCIII, high dose PCIII (10 mg/kg/day) was administered intraperitoneally to two-month-old mice. Following 7 days of PCIII treatment, PCIII distributed to various tissues, with substantial penetration into brains. The mice that were treated with high dose PCIII had no structural abnormalities in the major organs or neuroinflammation. In addition, high dose PCIII (10 mg/kg/day) in mice had no adverse impact on motor function. These findings suggest that PCIII has a relatively high therapeutic index. Given the favorable safety features of PCIII and neuroprotective function in the PD mouse model, it may become a promising disease-modifying therapy in PD to regulate pathogenic α-synuclein aggregation.

2 Article α-Synuclein accumulation and GBA deficiency due to L444P GBA mutation contributes to MPTP-induced parkinsonism. 2018

Yun, Seung Pil / Kim, Donghoon / Kim, Sangjune / Kim, SangMin / Karuppagounder, Senthilkumar S / Kwon, Seung-Hwan / Lee, Saebom / Kam, Tae-In / Lee, Suhyun / Ham, Sangwoo / Park, Jae Hong / Dawson, Valina L / Dawson, Ted M / Lee, Yunjong / Ko, Han Seok. ·Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Neurology, Baltimore, MD, USA. · Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, USA. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, South Korea. · Department of Physiology, Baltimore, MD, USA. · Solomon H. Snyder Department of Neuroscience, Baltimore, MD, USA. · Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Diana Helis Henry Medical Research Foundation, New Orleans, LA, USA. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, South Korea. ylee69@skku.edu. · Samsung Medical Center (SMC), Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, South Korea. ylee69@skku.edu. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. hko3@jhmi.edu. · Department of Neurology, Baltimore, MD, USA. hko3@jhmi.edu. · Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, USA. hko3@jhmi.edu. · Diana Helis Henry Medical Research Foundation, New Orleans, LA, USA. hko3@jhmi.edu. ·Mol Neurodegener · Pubmed #29310663.

ABSTRACT: BACKGROUND: Mutations in glucocerebrosidase (GBA) cause Gaucher disease (GD) and increase the risk of developing Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Since both genetic and environmental factors contribute to the pathogenesis of sporadic PD, we investigated the susceptibility of nigrostriatal dopamine (DA) neurons in L444P GBA heterozygous knock-in (GBA METHOD: We used GBA RESULTS: L444P GBA heterozygous mutation reduced GBA protein levels, enzymatic activity and a concomitant accumulation of α-synuclein in the midbrain of GBA CONCLUSION: Our results suggest that GBA deficiency due to L444P GBA heterozygous mutation and the accompanying accumulation of α-synuclein render DA neurons more susceptible to MPTP intoxication. Thus, GBA and α-synuclein play dual physiological roles in the survival of DA neurons in response to the mitochondrial dopaminergic neurotoxin, MPTP.

3 Article CRISPR-Cas9 Mediated Telomere Removal Leads to Mitochondrial Stress and Protein Aggregation. 2017

Kim, Hyojung / Ham, Sangwoo / Jo, Minkyung / Lee, Gum Hwa / Lee, Yun-Song / Shin, Joo-Ho / Lee, Yunjong. ·Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Gyeonggi-do 440-746, Korea. hjung93@skku.edu. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Gyeonggi-do 440-746, Korea. ham89p12@skku.edu. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Gyeonggi-do 440-746, Korea. jmk4606@naver.com. · College of Pharmacy, Chosun University, Gwangju 501-759, Korea. yslee@skku.edu. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Gyeonggi-do 440-746, Korea. gumhwalee@chosun.ac.kr. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Gyeonggi-do 440-746, Korea. jshin24@skku.edu. · Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 440-746, Korea. jshin24@skku.edu. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, Gyeonggi-do 440-746, Korea. ylee69@skku.edu. ·Int J Mol Sci · Pubmed #28972555.

ABSTRACT: Aging is considered the major risk factor for neurodegenerative diseases including Parkinson's disease (PD). Telomere shortening is associated with cellular senescence. In this regard, pharmacological or genetic inhibition of telomerase activity has been used to model cellular aging. Here, we employed CRISPR-Cas9 technology to instantly remove the telomere to induce aging in a neuroblastoma cell line. Expression of both Cas9 and guide RNA targeting telomere repeats ablated the telomere, leading to retardation of cell proliferation. Instant deletion of telomere in SH-SY5Y cells impaired mitochondrial function with diminished mitochondrial respiration and cell viability. Supporting the pathological relevance of cell aging by CRISPR-Cas9 mediated telomere removal, alterations were observed in the levels of PD-associated proteins including PTEN-induced putative kinase 1, peroxisome proliferator-activated receptor γ coactivator 1-α, nuclear respiratory factor 1, parkin, and aminoacyl tRNA synthetase complex interacting multifunctional protein 2. Significantly, α-synuclein expression in the background of telomere removal led to the enhancement of protein aggregation, suggesting positive feed-forward interaction between aging and PD pathogenesis. Collectively, our results demonstrate that CRISPR-Cas9 can be used to efficiently model cellular aging and PD.

4 Article Activation of the ATF2/CREB-PGC-1α pathway by metformin leads to dopaminergic neuroprotection. 2017

Kang, Hojin / Khang, Rin / Ham, Sangwoo / Jeong, Ga Ram / Kim, Hyojung / Jo, Minkyung / Lee, Byoung Dae / Lee, Yun Il / Jo, Areum / Park, ChiHu / Kim, Hyein / Seo, Jeongkon / Paek, Sun Ha / Lee, Yun-Song / Choi, Jeong-Yun / Lee, Yunjong / Shin, Joo-Ho. ·Department of Molecular Cell Biology, Division of Pharmacology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, South Korea. · Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, South Korea. · Department of Neuroscience, Department of Physiology, Neurodegeneration Control Research Center, Kyung Hee University School of Medicine, Seoul, South Korea. · Department of New Biology, Daegu Geongbuk Institute of Science and Technology, Daegu, South Korea. · Research Core Facility, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, South Korea. · HuGeX Co., Ltd. Seongnam, South Korea. · UNIST Central Research Facility, Ulsan National Institute of Science and Technology, Ulsan, South Korea. · Department of Neurosurgery, Seoul National University College of Medicine, Seoul, South Korea. ·Oncotarget · Pubmed #28611284.

ABSTRACT: Progressive dopaminergic neurodegeneration is responsible for the canonical motor deficits in Parkinson's disease (PD). The widely prescribed anti-diabetic medicine metformin is effective in preventing neurodegeneration in animal models; however, despite the significant potential of metformin for treating PD, the therapeutic effects and molecular mechanisms underlying dopaminergic neuroprotection by metformin are largely unknown.In this study, we found that metformin induced substantial proteomic changes, especially in metabolic and mitochondrial pathways in the substantia nigra (SN). Consistent with this data, metformin increased mitochondrial marker proteins in SH-SY5Y neuroblastoma cells. Mitochondrial protein expression by metformin was found to be brain region specific, with metformin increasing mitochondrial proteins in the SN and the striatum, but not the cortex. As a potential upstream regulator of mitochondria gene transcription by metformin, PGC-1α promoter activity was stimulated by metformin via CREB and ATF2 pathways. PGC-1α and phosphorylation of ATF2 and CREB by metformin were selectively increased in the SN and the striatum, but not the cortex. Finally, we showed that metformin protected dopaminergic neurons and improved dopamine-sensitive motor performance in an MPTP-induced PD animal model. Together these results suggest that the metformin-ATF2/CREB-PGC-1α pathway might be promising therapeutic target for PD.

5 Article VPS35 regulates parkin substrate AIMP2 toxicity by facilitating lysosomal clearance of AIMP2. 2017

Yun, Seung Pil / Kim, Hyojung / Ham, Sangwoo / Kwon, Seung-Hwan / Lee, Gum Hwa / Shin, Joo-Ho / Lee, Sang Hun / Ko, Han Seok / Lee, Yunjong. ·Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, USA. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon, South Korea. · College of Pharmacy, Chosun University, Gwangju, Republic of Korea. · Medical Science Research Institute, Soonchunhyang University, Seoul Hospital, Seoul, Republic of Korea. · Diana Helis Henry Medical Research Foundation, New Orleans, LA, USA. ·Cell Death Dis · Pubmed #28383562.

ABSTRACT: Vacuolar protein sorting-associated protein 35 (VPS35) is involved in retrograde transport of proteins from endosomes to trans-Golgi network. Gene mutations in VPS35 are linked to autosomal dominant late-onset Parkinson's disease (PD). Although the identification of VPS35 mutations has provided novel insight about its interactions with several PD-associated genes including leucine-rich repeat kinase 2 (LRRK2) and α-synuclein, little information is available about the molecular mechanisms of cell death downstream of VPS35 dysfunction. In this study, we showed that VPS35 has a role in the lysosomal degradation of parkin substrate aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2), of which accumulation leads to poly(ADP-ribose) polymerase-1 (PARP1)-dependent cell death. VPS35 was co-immunoprecipitated with AIMP2, as well as lysosome-associated membrane protein-2a (Lamp2a). Interestingly, this association was disrupted by PD-associated VPS35 mutant D620N. VPS35 overexpression prevented AIMP2-potentiated cell death and PARP1 activation in SH-SY5Y cells. More importantly, knockdown of VPS35 led to PARP1 activation and cell death, which was AIMP2 dependent. These findings provide new mechanistic insights into the role of VPS35 in the regulation of AIMP2 levels and cell death. As AIMP2 accumulation was reported in PD patient's brains and involved in dopaminergic cell death, identification of VPS35 as a novel regulator of AIMP2 clearance via lysosomal pathway provides alternative venue to control dopaminergic cell death in PD.

6 Article Hydrocortisone-induced parkin prevents dopaminergic cell death via CREB pathway in Parkinson's disease model. 2017

Ham, Sangwoo / Lee, Yun-Il / Jo, Minkyung / Kim, Hyojung / Kang, Hojin / Jo, Areum / Lee, Gum Hwa / Mo, Yun Jeong / Park, Sang Chul / Lee, Yun Song / Shin, Joo-Ho / Lee, Yunjong. ·Division of Pharmacology, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do, 440-746, Republic of Korea. · Well Aging Research Center, DGIST, Daegu, 42988, Republic of Korea. ylee56@dgist.ac.kr. · Companion Diagnostics and Medical Technology Research Group, DGIST, Daegu, 42988, Republic of Korea. ylee56@dgist.ac.kr. · College of Pharmacy, Chosun University, Gwangju, 501-759, Republic of Korea. · Well Aging Research Center, DGIST, Daegu, 42988, Republic of Korea. · Division of Pharmacology, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do, 440-746, Republic of Korea. jshin24@skku.edu. · Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do, 440-746, Republic of Korea. jshin24@skku.edu. · Division of Pharmacology, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do, 440-746, Republic of Korea. ylee69@skku.edu. ·Sci Rep · Pubmed #28366931.

ABSTRACT: Dysfunctional parkin due to mutations or post-translational modifications contributes to dopaminergic neurodegeneration in Parkinson's disease (PD). Overexpression of parkin provides protection against cellular stresses and prevents dopamine cell loss in several PD animal models. Here we performed an unbiased high-throughput luciferase screening to identify chemicals that can increase parkin expression. Among promising parkin inducers, hydrocortisone possessed the most favorable profiles including parkin induction ability, cell protection ability, and physicochemical property of absorption, distribution, metabolism, and excretion (ADME) without inducing endoplasmic reticulum stress. We found that hydrocortisone-induced parkin expression was accountable for cell protection against oxidative stress. Hydrocortisone-activated parkin expression was mediated by CREB pathway since gRNA to CREB abolished hydrocortisone's ability to induce parkin. Finally, hydrocortisone treatment in mice increased brain parkin levels and prevented 6-hydroxy dopamine induced dopamine cell loss when assessed at 4 days after the toxin's injection. Our results showed that hydrocortisone could stimulate parkin expression via CREB pathway and the induced parkin expression was accountable for its neuroprotective effect. Since glucocorticoid is a physiological hormone, maintaining optimal levels of glucocorticoid might be a potential therapeutic or preventive strategy for Parkinson's disease.

7 Article PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival. 2017

Lee, Yunjong / Stevens, Daniel A / Kang, Sung-Ung / Jiang, Haisong / Lee, Yun-Il / Ko, Han Seok / Scarffe, Leslie A / Umanah, George E / Kang, Hojin / Ham, Sangwoo / Kam, Tae-In / Allen, Kathleen / Brahmachari, Saurav / Kim, Jungwoo Wren / Neifert, Stewart / Yun, Seung Pil / Fiesel, Fabienne C / Springer, Wolfdieter / Dawson, Valina L / Shin, Joo-Ho / Dawson, Ted M. ·Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, South Korea. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA; Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130-2685, USA. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, South Korea. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Mayo Graduate School, Neurobiology of Disease, Mayo Clinic, Jacksonville, FL 32224, USA. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA; Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130-2685, USA. Electronic address: vdawson@jhmi.edu. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, South Korea. Electronic address: jshin24@skku.edu. · Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA 70130-2685, USA; Diana Helis Henry Medical Research Foundation, New Orleans, LA 70130-2685, USA. Electronic address: tdawson@jhmi.edu. ·Cell Rep · Pubmed #28122242.

ABSTRACT: Mutations in PTEN-induced putative kinase 1 (PINK1) and parkin cause autosomal-recessive Parkinson's disease through a common pathway involving mitochondrial quality control. Parkin inactivation leads to accumulation of the parkin interacting substrate (PARIS, ZNF746) that plays an important role in dopamine cell loss through repression of proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α) promoter activity. Here, we show that PARIS links PINK1 and parkin in a common pathway that regulates dopaminergic neuron survival. PINK1 interacts with and phosphorylates serines 322 and 613 of PARIS to control its ubiquitination and clearance by parkin. PINK1 phosphorylation of PARIS alleviates PARIS toxicity, as well as repression of PGC-1α promoter activity. Conditional knockdown of PINK1 in adult mouse brains leads to a progressive loss of dopaminergic neurons in the substantia nigra that is dependent on PARIS. Altogether, these results uncover a function of PINK1 to direct parkin-PARIS-regulated PGC-1α expression and dopaminergic neuronal survival.