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Article ; Online: De novo variants cause complex symptoms in HSP-ATL1 (SPG3A) and uncover genotype-phenotype correlations.

Alecu, Julian E / Saffari, Afshin / Jordan, Catherine / Srivastava, Siddharth / Blackstone, Craig / Ebrahimi-Fakhari, Darius

Human molecular genetics

2022 Volume 32, Issue 1, Page(s) 93–103

Abstract: Pathogenic variants in ATL1 are a known cause of autosomal-dominantly inherited hereditary spastic paraplegia (HSP-ATL1, SPG3A) with a predominantly 'pure' HSP phenotype. Although a relatively large number of patients have been reported, no genotype- ... ...

Abstract	Pathogenic variants in ATL1 are a known cause of autosomal-dominantly inherited hereditary spastic paraplegia (HSP-ATL1, SPG3A) with a predominantly 'pure' HSP phenotype. Although a relatively large number of patients have been reported, no genotype-phenotype correlations have been established for specific ATL1 variants. Confronted with five children carrying de novo ATL1 variants showing early, complex and severe symptoms, we systematically investigated the molecular and phenotypic spectrum of HSP-ATL1. Through a cross-sectional analysis of 537 published and novel cases, we delineate a distinct phenotype observed in patients with de novo variants. Guided by this systematic phenotyping approach and structural modelling of disease-associated variants in atlastin-1, we demonstrate that this distinct phenotypic signature is also prevalent in a subgroup of patients with inherited ATL1 variants and is largely explained by variant localization within a three-dimensional mutational cluster. Establishing genotype-phenotype correlations, we find that symptoms that extend well beyond the typical pure HSP phenotype (i.e. neurodevelopmental abnormalities, upper limb spasticity, bulbar symptoms, peripheral neuropathy and brain imaging abnormalities) are prevalent in patients with variants located within this mutational cluster.
MeSH term(s)	Humans ; Cross-Sectional Studies ; DNA Mutational Analysis ; GTP-Binding Proteins/genetics ; Membrane Proteins/genetics ; Mutation ; Pedigree ; Phenotype ; Spastic Paraplegia, Hereditary/genetics ; Spastic Paraplegia, Hereditary/pathology
Chemical Substances	GTP-Binding Proteins (EC 3.6.1.-) ; Membrane Proteins ; ATL1 protein, human (EC 3.6.1.-)
Language	English
Publishing date	2022-08-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddac182
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Article: Disease Severity and Motor Impairment Correlate With Health-Related Quality of Life in AP-4-Associated Hereditary Spastic Paraplegia.

Jordan, Catherine / Geisel, Gregory / Alecu, Julian E / Zhang, Bo / Sahin, Mustafa / Ebrahimi-Fakhari, Darius

Neurology. Genetics

2021 Volume 7, Issue 4, Page(s) e605

Abstract: Objective: AP-4-associated hereditary spastic paraplegia (AP-4-HSP) is a childhood-onset neurogenetic disease and mimic of cerebral palsy. Data on health-related quality of life (HRQoL) are lacking. To establish a metric for HRQoL and caregiver ... ...

Abstract	Objective: AP-4-associated hereditary spastic paraplegia (AP-4-HSP) is a childhood-onset neurogenetic disease and mimic of cerebral palsy. Data on health-related quality of life (HRQoL) are lacking. To establish a metric for HRQoL and caregiver priorities, we used the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire to assess HRQoL in correlation with disease severity in 64 patients with AP-4-HSP. Methods: A cross-sectional analysis of caregiver-reported HRQoL was performed using the CPCHILD questionnaire in combination with a detailed clinical characterization. Results: HRQoL was impaired in all domains in patients with AP-4-HSP (mean score: 59.6 ± 12.6 [SD]), with no significant difference between the 4 subtypes. Age, as a surrogate for disease duration, and Spastic Paraplegia Rating Scale scores, as an indicator for corticospinal tract dysfunction and motor impairment, correlated with lower CPCHILD scores (Pearson Conclusions: We show that the CPCHILD questionnaire, developed for use in children with cerebral palsy, can be used to assess HRQoL in patients with childhood-onset complex hereditary spastic paraplegia. HRQoL is reduced in patients with AP-4-HSP and correlates with the degree of motor impairment. These results provide a framework for medical decision making and a baseline for the future development of treatment guidelines and interventional trials.
Language	English
Publishing date	2021-07-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2818607-2
ISSN	2376-7839
ISSN	2376-7839
DOI	10.1212/NXG.0000000000000605
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Article ; Online: Generation and characterization of six human induced pluripotent stem cell lines (iPSC) from three families with AP4M1-associated hereditary spastic paraplegia (SPG50).

Eberhardt, Kathrin / Jumo, Hellen / D'Amore, Angelica / Alecu, Julian E / Ziegler, Marvin / Afshar Saber, Wardiya / Sahin, Mustafa / Ebrahimi-Fakhari, Darius

Stem cell research

2021 Volume 53, Page(s) 102335

Abstract: Biallelic loss-of-function variants in the subunits of the adaptor protein complex 4 lead to childhood-onset hereditary spastic paraplegia (AP-4-HSP): SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1), and SPG52 (AP4S1). Here, we describe the generation of ... ...

Abstract	Biallelic loss-of-function variants in the subunits of the adaptor protein complex 4 lead to childhood-onset hereditary spastic paraplegia (AP-4-HSP): SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1), and SPG52 (AP4S1). Here, we describe the generation of induced pluripotent stem cells (iPSCs) from three AP-4-HSP patients with biallelic, loss-of-function variants in AP4M1 and their sex-matched parents (asymptomatic, heterozygous carriers). Following reprogramming using non-integrating Sendai virus, iPSCs were characterized following standard protocols including karyotyping, embryoid body formation, pluripotency marker expression and STR profiling. These first iPSC lines for SPG50 provide a valuable resource for studying this rare disease and related forms of hereditary spastic paraplegia.
MeSH term(s)	Adaptor Protein Complex 4/genetics ; Cerebral Palsy ; Child ; Heterozygote ; Humans ; Induced Pluripotent Stem Cells ; Spastic Paraplegia, Hereditary/genetics
Chemical Substances	Adaptor Protein Complex 4
Language	English
Publishing date	2021-04-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2393143-7
ISSN	1876-7753 ; 1873-5061
ISSN (online)	1876-7753
ISSN	1873-5061
DOI	10.1016/j.scr.2021.102335
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Article ; Online: High-content screening identifies a small molecule that restores AP-4-dependent protein trafficking in neuronal models of AP-4-associated hereditary spastic paraplegia.

Saffari, Afshin / Brechmann, Barbara / Böger, Cedric / Saber, Wardiya Afshar / Jumo, Hellen / Whye, Dosh / Wood, Delaney / Wahlster, Lara / Alecu, Julian E / Ziegler, Marvin / Scheffold, Marlene / Winden, Kellen / Hubbs, Jed / Buttermore, Elizabeth D / Barrett, Lee / Borner, Georg H H / Davies, Alexandra K / Ebrahimi-Fakhari, Darius / Sahin, Mustafa

Nature communications

2024 Volume 15, Issue 1, Page(s) 584

Abstract: Unbiased phenotypic screens in patient-relevant disease models offer the potential to detect therapeutic targets for rare diseases. In this study, we developed a high-throughput screening assay to identify molecules that correct aberrant protein ... ...

Abstract	Unbiased phenotypic screens in patient-relevant disease models offer the potential to detect therapeutic targets for rare diseases. In this study, we developed a high-throughput screening assay to identify molecules that correct aberrant protein trafficking in adapter protein complex 4 (AP-4) deficiency, a rare but prototypical form of childhood-onset hereditary spastic paraplegia characterized by mislocalization of the autophagy protein ATG9A. Using high-content microscopy and an automated image analysis pipeline, we screened a diversity library of 28,864 small molecules and identified a lead compound, BCH-HSP-C01, that restored ATG9A pathology in multiple disease models, including patient-derived fibroblasts and induced pluripotent stem cell-derived neurons. We used multiparametric orthogonal strategies and integrated transcriptomic and proteomic approaches to delineate potential mechanisms of action of BCH-HSP-C01. Our results define molecular regulators of intracellular ATG9A trafficking and characterize a lead compound for the treatment of AP-4 deficiency, providing important proof-of-concept data for future studies.
MeSH term(s)	Humans ; Spastic Paraplegia, Hereditary/drug therapy ; Spastic Paraplegia, Hereditary/genetics ; Spastic Paraplegia, Hereditary/metabolism ; Proteomics ; Neurons/metabolism ; Protein Transport ; Proteins/metabolism ; Mutation
Chemical Substances	Proteins
Language	English
Publishing date	2024-01-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-44264-1
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Article ; Online: Plasma Neurofilament Light Chain Is Elevated in Adaptor Protein Complex 4-Related Hereditary Spastic Paraplegia.

Alecu, Julian E / Saffari, Afshin / Ziegler, Marvin / Jordan, Catherine / Tam, Amy / Kim, Soyoung / Leung, Edward / Szczaluba, Krzysztof / Mierzewska, Hanna / King, Staci D / Santorelli, Filippo M / Yoon, Grace / Trombetta, Bianca / Kivisäkk, Pia / Zhang, Bo / Sahin, Mustafa / Ebrahimi-Fakhari, Darius

Movement disorders : official journal of the Movement Disorder Society

2023 Volume 38, Issue 9, Page(s) 1742–1750

Abstract: Background: Adaptor protein complex 4-associated hereditary spastic paraplegia (AP-4-HSP) is caused by pathogenic biallelic variants in AP4B1, AP4M1, AP4E1, and AP4S1.: Objective: The aim was to explore blood markers of neuroaxonal damage in AP-4-HSP. ...

Abstract	Background: Adaptor protein complex 4-associated hereditary spastic paraplegia (AP-4-HSP) is caused by pathogenic biallelic variants in AP4B1, AP4M1, AP4E1, and AP4S1. Objective: The aim was to explore blood markers of neuroaxonal damage in AP-4-HSP. Methods: Plasma neurofilament light chain (pNfL) and glial fibrillary acidic protein (GFAP) levels were measured in samples from patients and age- and sex-matched controls (NfL: n = 46 vs. n = 46; GFAP: n = 14 vs. n = 21) using single-molecule array assays. Patients' phenotypes were systematically assessed using the AP-4-HSP natural history study questionnaires, the Spastic Paraplegia Rating Scale, and the SPATAX disability score. Results: pNfL levels increased in AP-4-HSP patients, allowing differentiation from controls (Mann-Whitney U test: P = 3.0e-10; area under the curve = 0.87 with a 95% confidence interval of 0.80-0.94). Phenotypic cluster analyses revealed a subgroup of individuals with severe generalized-onset seizures and developmental stagnation, who showed differentially higher pNfL levels (Mann-Whitney U test between two identified clusters: P = 2.5e-6). Plasma GFAP levels were unchanged in patients with AP-4-HSP. Conclusions: pNfL is a potential disease marker in AP-4-HSP and can help differentiate between phenotypic subgroups. © 2023 International Parkinson and Movement Disorder Society.
MeSH term(s)	Humans ; Adaptor Protein Complex 4/genetics ; Spastic Paraplegia, Hereditary/genetics ; Intermediate Filaments/metabolism ; Phenotype ; Mutation
Chemical Substances	Adaptor Protein Complex 4
Language	English
Publishing date	2023-07-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.29524
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Zs.A 2555: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: AP-4-mediated axonal transport controls endocannabinoid production in neurons.

Davies, Alexandra K / Alecu, Julian E / Ziegler, Marvin / Vasilopoulou, Catherine G / Merciai, Fabrizio / Jumo, Hellen / Afshar-Saber, Wardiya / Sahin, Mustafa / Ebrahimi-Fakhari, Darius / Borner, Georg H H

Nature communications

2022 Volume 13, Issue 1, Page(s) 1058

Abstract: The adaptor protein complex AP-4 mediates anterograde axonal transport and is essential for axon health. AP-4-deficient patients suffer from a severe neurodevelopmental and neurodegenerative disorder. Here we identify DAGLB (diacylglycerol lipase-beta), ... ...

Abstract	The adaptor protein complex AP-4 mediates anterograde axonal transport and is essential for axon health. AP-4-deficient patients suffer from a severe neurodevelopmental and neurodegenerative disorder. Here we identify DAGLB (diacylglycerol lipase-beta), a key enzyme for generation of the endocannabinoid 2-AG (2-arachidonoylglycerol), as a cargo of AP-4 vesicles. During normal development, DAGLB is targeted to the axon, where 2-AG signalling drives axonal growth. We show that DAGLB accumulates at the trans-Golgi network of AP-4-deficient cells, that axonal DAGLB levels are reduced in neurons from a patient with AP-4 deficiency, and that 2-AG levels are reduced in the brains of AP-4 knockout mice. Importantly, we demonstrate that neurite growth defects of AP-4-deficient neurons are rescued by inhibition of MGLL (monoacylglycerol lipase), the enzyme responsible for 2-AG hydrolysis. Our study supports a new model for AP-4 deficiency syndrome in which axon growth defects arise through spatial dysregulation of endocannabinoid signalling.
MeSH term(s)	Adaptor Protein Complex 4/metabolism ; Animals ; Axonal Transport ; Axons/metabolism ; Endocannabinoids/metabolism ; Humans ; Mice ; Monoacylglycerol Lipases/genetics ; Monoacylglycerol Lipases/metabolism ; Neurons/metabolism
Chemical Substances	Adaptor Protein Complex 4 ; Endocannabinoids ; Monoacylglycerol Lipases (EC 3.1.1.23)
Language	English
Publishing date	2022-02-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-28609-w
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Article ; Online: Novel CAPN1 missense variants in complex hereditary spastic paraplegia with early-onset psychosis.

Alecu, Julian E / Saffari, Afshin / Jumo, Hellen / Ziegler, Marvin / Strelko, Oleksandr / Brownstein, Catherine A / Gonzalez-Heydrich, Joseph / Rodan, Lance H / Gorman, Mark P / Sahin, Mustafa / Ebrahimi-Fakhari, Darius

Annals of clinical and translational neurology

2022 Volume 9, Issue 4, Page(s) 570–576

Abstract: CAPN1-associated hereditary spastic paraplegia (SPG76) is a rare and clinically heterogenous syndrome due to loss of calpain-1 function. Here we illustrate a translational approach to the case of an 18-year-old patient who first presented with ... ...

Abstract	CAPN1-associated hereditary spastic paraplegia (SPG76) is a rare and clinically heterogenous syndrome due to loss of calpain-1 function. Here we illustrate a translational approach to the case of an 18-year-old patient who first presented with psychiatric symptoms followed by spastic gait, intention tremor, and neurogenic bladder dysfunction, consistent with a complex form of HSP. Exome sequencing showed compound-heterozygous missense variants in CAPN1 (NM_001198868.2: c.1712A>G (p.Asn571Ser)/c.1991C>T (p.Ser664Leu)) and a previously reported heterozygous stop-gain variant in RCL1. In silico analyses of the CAPN1 variants predicted a deleterious effect and in vitro functional studies confirmed reduced calpain-1 activity and dysregulated downstream signaling. These findings support a diagnosis of SPG76 and highlight that the psychiatric symptoms can precede the motor symptoms in HSP. Our results also suggest that multiple genes can potentially contribute to complex neuropsychiatric diseases.
MeSH term(s)	Adolescent ; Calpain/genetics ; Humans ; Mutation ; Pedigree ; Psychotic Disorders/genetics ; Spastic Paraplegia, Hereditary/genetics
Chemical Substances	Calpain (EC 3.4.22.-) ; CAPN1 protein, human (EC 3.4.22.52)
Language	English
Publishing date	2022-03-16
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.51531
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Article ; Online: Systematic Analysis of Brain MRI Findings in Adaptor Protein Complex 4-Associated Hereditary Spastic Paraplegia.

Ebrahimi-Fakhari, Darius / Alecu, Julian E / Ziegler, Marvin / Geisel, Gregory / Jordan, Catherine / D'Amore, Angelica / Yeh, Rebecca C / Akula, Shyam K / Saffari, Afshin / Prabhu, Sanjay P / Sahin, Mustafa / Yang, Edward

Neurology

2021 Volume 97, Issue 19, Page(s) e1942–e1954

Abstract: Background and objectives: AP-4-associated hereditary spastic paraplegia (AP-4-HSP: SPG47, SPG50, SPG51, SPG52) is an emerging cause of childhood-onset hereditary spastic paraplegia and mimic of cerebral palsy. This study aims to define the spectrum of ... ...

Abstract	Background and objectives: AP-4-associated hereditary spastic paraplegia (AP-4-HSP: SPG47, SPG50, SPG51, SPG52) is an emerging cause of childhood-onset hereditary spastic paraplegia and mimic of cerebral palsy. This study aims to define the spectrum of brain MRI findings in AP-4-HSP and to investigate radioclinical correlations. Methods: We performed a systematic qualitative and quantitative analysis of 107 brain MRI studies from 76 individuals with genetically confirmed AP-4-HSP and correlation with clinical findings including surrogates of disease severity. Results: We define AP-4-HSP as a disorder of gray and white matter and demonstrate that abnormal myelination is common and that metrics of reduced white matter volume correlate with severity of motor symptoms. We identify a common diagnostic imaging signature consisting of (1) a thin splenium of the corpus callosum, (2) an absent or thin anterior commissure, (3) characteristic signal abnormalities of the forceps minor ("ears of the grizzly sign"), and (4) periventricular white matter abnormalities. The presence of 2 or more of these findings has a sensitivity of ∼99% for detecting AP-4-HSP; the combination of all 4 is found in ∼45% of cases. Compared to other HSPs with a thin corpus callosum, the absent anterior commissure appears to be specific to AP-4-HSP. Our analysis identified a subset of patients with polymicrogyria, underscoring the role of AP-4 in early brain development. These patients displayed a higher prevalence of seizures and status epilepticus, many at a young age. Discussion: Our findings define the MRI spectrum of AP-4-HSP, providing opportunities for early diagnosis, identification of individuals at risk for complications, and a window into the role of the AP-4 complex in brain development and neurodegeneration.
MeSH term(s)	Adaptor Protein Complex 4/metabolism ; Corpus Callosum/diagnostic imaging ; Corpus Callosum/metabolism ; Humans ; Magnetic Resonance Imaging/methods ; Neuroimaging ; Spastic Paraplegia, Hereditary/diagnostic imaging ; Spastic Paraplegia, Hereditary/metabolism
Chemical Substances	Adaptor Protein Complex 4
Language	English
Publishing date	2021-09-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000012836
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Article ; Online: Quantitative retrospective natural history modeling of

Saffari, Afshin / Schröter, Julian / Garbade, Sven F / Alecu, Julian E / Ebrahimi-Fakhari, Darius / Hoffmann, Georg F / Kölker, Stefan / Ries, Markus / Syrbe, Steffen

Autophagy

2021 Volume 18, Issue 7, Page(s) 1715–1727

Abstract: ... ...

Abstract	WDR45
MeSH term(s)	Autophagy/physiology ; Brain Diseases/genetics ; Carrier Proteins/genetics ; Cross-Sectional Studies ; Delayed Diagnosis ; Female ; Humans ; Infant ; Male ; Retrospective Studies
Chemical Substances	Carrier Proteins ; WDR45 protein, human
Language	English
Publishing date	2021-11-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.1080/15548627.2021.1990671
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Zs.A 6741: Show issues

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Article ; Online: Demonstration of brain region-specific neuronal vulnerability in human iPSC-based model of familial Parkinson's disease.

Brazdis, Razvan-Marius / Alecu, Julian E / Marsch, Daniel / Dahms, Annika / Simmnacher, Katrin / Lörentz, Sandra / Brendler, Anna / Schneider, Yanni / Marxreiter, Franz / Roybon, Laurent / Winner, Beate / Xiang, Wei / Prots, Iryna

Human molecular genetics

2020 Volume 29, Issue 7, Page(s) 1180–1191

Abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein inclusions mostly composed of aggregated forms of α-synuclein (α-Syn) and by the progressive degeneration of midbrain dopaminergic neurons (mDANs), resulting in motor ... ...

Abstract	Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein inclusions mostly composed of aggregated forms of α-synuclein (α-Syn) and by the progressive degeneration of midbrain dopaminergic neurons (mDANs), resulting in motor symptoms. While other brain regions also undergo pathologic changes in PD, the relevance of α-Syn aggregation for the preferential loss of mDANs in PD pathology is not completely understood yet. To elucidate the mechanisms of the brain region-specific neuronal vulnerability in PD, we modeled human PD using human-induced pluripotent stem cells (iPSCs) from familial PD cases with a duplication (Dupl) of the α-Syn gene (SNCA) locus. Human iPSCs from PD Dupl patients and a control individual were differentiated into mDANs and cortical projection neurons (CPNs). SNCA dosage increase did not influence the differentiation efficiency of mDANs and CPNs. However, elevated α-Syn pathology, as revealed by enhanced α-Syn insolubility and phosphorylation, was determined in PD-derived mDANs compared with PD CPNs. PD-derived mDANs exhibited higher levels of reactive oxygen species and protein nitration levels compared with CPNs, which might underlie elevated α-Syn pathology observed in mDANs. Finally, increased neuronal death was observed in PD-derived mDANs compared to PD CPNs and to control mDANs and CPNs. Our results reveal, for the first time, a higher α-Syn pathology, oxidative stress level, and neuronal death rate in human PD mDANs compared with PD CPNs from the same patient. The finding implies the contribution of pathogenic α-Syn, probably induced by oxidative stress, to selective vulnerability of substantia nigra dopaminergic neurons in human PD.
MeSH term(s)	Brain/growth & development ; Brain/metabolism ; Brain/pathology ; Cell Death/genetics ; Cell Differentiation/genetics ; Cell Line ; Dopaminergic Neurons/metabolism ; Dopaminergic Neurons/pathology ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/transplantation ; Mesencephalon/metabolism ; Mesencephalon/pathology ; Neurites/metabolism ; Neurites/pathology ; Oxidative Stress/genetics ; Parkinson Disease/genetics ; Parkinson Disease/metabolism ; Parkinson Disease/therapy ; Substantia Nigra/metabolism ; Substantia Nigra/pathology ; alpha-Synuclein/genetics
Chemical Substances	alpha-Synuclein
Language	English
Publishing date	2020-03-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddaa039
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