Featured
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Article |
Structural insights into vesicular monoamine storage and drug interactions
Monoamines and neurotoxicants share a binding pocket in VMAT1 featuring polar sites for specificity and a wrist-and-fist shape for versatility, and monoamine enrichment in storage vesicles arises from dominant import via favoured lumenal-open transition of VMAT1 and protonation-precluded binding during its cytoplasmic-open transition.
- Jin Ye
- , Huaping Chen
- & Weikai Li
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News |
Spinal implant helps man with advanced Parkinson’s to walk without falling
Electrical stimulation improved his mobility, although researchers say that a larger study is needed to assess the device.
- Emily Waltz
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Article |
Co-transplantation of autologous Treg cells in a cell therapy for Parkinson’s disease
In mouse and rat models of Parkinson’s disease, co-transplanting regulatory T cells (Treg cells) improves the survival of grafted midbrain dopamine neurons in cell therapies by reducing the inflammatory response caused by surgical injury.
- Tae-Yoon Park
- , Jeha Jeon
- & Kwang-Soo Kim
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Matters Arising |
Ptbp1 deletion does not induce astrocyte-to-neuron conversion
- Thanh Hoang
- , Dong Won Kim
- & Seth Blackshaw
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Article |
Structures of α-synuclein filaments from human brains with Lewy pathology
The authors report on the structures of α-synuclein filaments from the brains of individuals with Parkinson's disease, Parkinson's disease dementia and dementia with Lewy bodies and how they differ from those seen in multiple system atrophy.
- Yang Yang
- , Yang Shi
- & Michel Goedert
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Research Briefing |
Tracing the brain circuitry underlying movement and mood symptoms in Parkinson’s disease
Parkinson’s disease causes slowness of movement, tremor and stiffness, along with mood symptoms such as depression. The brain’s parafascicular thalamus is shown to contain distinct neural circuits for locomotion, motor learning and depression-like states, and targeting these circuits alleviates some deficits in a mouse model of the disease.
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Article |
Targeting thalamic circuits rescues motor and mood deficits in PD mice
- Ying Zhang
- , Dheeraj S. Roy
- & Guoping Feng
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News & Views |
Mice with disrupted mitochondria used to model Parkinson’s disease
Mice in which organelles called mitochondria are disrupted in vulnerable neuronal cells provide a new model of Parkinson’s disease. The pattern of neurodegeneration challenges long-held ideas about the disease’s motor symptoms.
- Zak Doric
- & Ken Nakamura
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Article |
Disruption of mitochondrial complex I induces progressive parkinsonism
Dysfunction of mitochondrial complex I in mice is sufficient to cause progressive parkinsonism in which the loss of nigral dopamine release critically contributes to motor dysfunction.
- Patricia González-Rodríguez
- , Enrico Zampese
- & D. James Surmeier
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Outlook |
The promise and potential of stem cells in Parkinson’s disease
Treatments that replace lost neurons and restore normal movement have entered clinical trials, but these therapies could offer more relief than cure.
- Lauren Gravitz
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Article |
A growth-factor-activated lysosomal K+ channel regulates Parkinson’s pathology
The identification of a lysosomal K+ channel complex—comprising AKT and the pore-forming TMEM175—provides insights into the mechanisms through which variants of the pore-forming protein affect the development of Parkinson’s disease.
- Jinhong Wie
- , Zhenjiang Liu
- & Dejian Ren
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Article |
Structure of LRRK2 in Parkinson’s disease and model for microtubule interaction
The structure of the catalytic half of LRRK2 and an atomic model of microtubule-associated LRRK2 suggest that the conformation of the kinase controls the association of LRRK2 with microtubules.
- C. K. Deniston
- , J. Salogiannis
- & A. E. Leschziner
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News & Views |
Method to combat Parkinson’s disease by astrocyte-to-neuron conversion
Astrocytes are non-neuronal brain cells that express a protein called PTB. It emerges that PTB depletion unlocks the potential of astrocytes to convert to neurons in a mouse model of Parkinson’s disease.
- Ernest Arenas
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Article |
Reversing a model of Parkinson’s disease with in situ converted nigral neurons
Depletion of the RNA-binding protein PTB (also known as PTBP1) in astrocytes reprograms these cells to become functional neurons and, in a mouse model of Parkinson’s disease, reverses the disease phenotype.
- Hao Qian
- , Xinjiang Kang
- & Xiang-Dong Fu
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News & Views |
Parkinson’s disease grafts benefit from well-timed growth factor
Grafts of stem-cell-derived precursors of dopamine neurons could be used to treat Parkinson’s disease, but this approach has limitations. Injecting a growth factor three weeks after transplantation can overcome some of these limits.
- Lorenz Studer
- & Viviane Tabar
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Article |
Discriminating α-synuclein strains in Parkinson’s disease and multiple system atrophy
Protein misfolding cyclic amplification (PMCA) technology can discriminate between patients with Parkinson’s disease and patients with multiple system atrophy on the basis of the characteristics of the α-synuclein aggregates in the cerebrospinal fluid.
- Mohammad Shahnawaz
- , Abhisek Mukherjee
- & Claudio Soto
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Article |
ATP13A2 deficiency disrupts lysosomal polyamine export
The lysosomal polyamine transporter ATP13A2 controls the cellular polyamine content, and impaired lysosomal polyamine export represents a lysosome-dependent cell death pathway that may be implicated in ATP13A2-associated neurodegeneration.
- Sarah van Veen
- , Shaun Martin
- & Peter Vangheluwe
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News & Views |
Infection triggers symptoms similar to those of Parkinson’s disease in mice lacking PINK1 protein
In mice lacking a protein genetically linked to Parkinson’s disease, an autoimmune response to gut infection compromises the function of dopamine-producing neurons and leads to transient movement impairments.
- Mary K. Herrick
- & Malú G. Tansey
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Letter |
Intestinal infection triggers Parkinson’s disease-like symptoms in Pink1−/− mice
In mice lacking PINK1, bacterial infection in the intestine results in mitochondrial antigen presentation and generation of CD8+ T cells, and infected mice develop motor impairments, suggesting that PINK1 suppresses autoimmunity.
- Diana Matheoud
- , Tyler Cannon
- & Michel Desjardins
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News & Views |
Elusive mitochondrial connection to inflammation uncovered
PINK1 and parkin proteins help to degrade damaged mitochondrial organelles, and abnormalities in these proteins are linked to Parkinson’s disease. Mouse studies reveal that the proteins act to prevent inflammation.
- Alexandra Stolz
- & Ivan Dikic
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Letter |
Cellular milieu imparts distinct pathological α-synuclein strains in α-synucleinopathies
Distinct strains of misfolded α-synuclein proteins, which aggregate in neurons in Lewy body diseases or in oligodendrocytes in multiple system atrophy, are formed as a consequence of differences between intracellular environments.
- Chao Peng
- , Ronald J. Gathagan
- & Virginia M.-Y. Lee
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News & Views |
Models of Parkinson’s disease revisited
Conventional models propose that activity levels in two neuronal pathways, which have opposing effects on movement, become imbalanced in Parkinson’s disease. Analyses in mice point to a more complex reality.
- Thomas Wichmann
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News & Views |
Vivid views of the PINK1 protein
Structures of an unusual enzymatic domain in PINK1 provide insights into how this protein regulates the function of organelles called mitochondria, and how mutations in PINK1 contribute to Parkinson’s disease.
- Salima Daou
- & Frank Sicheri
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News |
Trials of embryonic stem cells to launch in China
Studies to treat vision loss and Parkinson’s disease are the first to proceed under new regulations.
- David Cyranoski
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News |
Lab-grown blood stem cells produced at last
Two research teams cook up recipe to make long-sought cells in mice and people.
- Amy Maxmen
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Outlook |
Parkinson's disease: 4 big questions
The characteristic brain pathology and motor symptoms of Parkinson's disease are well established. But the details of the disease's cause and course are much murkier.
- Sarah Deweerdt
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Outlook |
Electrotherapy: Shock value
Deep brain stimulation is a proven treatment for Parkinson's disease. The only thing left to find out is how it works.
- Michael Eisenstein
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Outlook |
Technology: Monitoring gets personal
By bootstrapping existing technologies, researchers can gain a minute-by-minute understanding of a patient's disease.
- Lauren Gravitz
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Outlook |
Two hundred steps
In the 200 years since Parkinson's disease was first described, the understanding and management of the disease has come a long way. But researchers have yet to unlock all of its secrets. By Liam Drew.
- Liam Drew
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Outlook |
Perspective: Data sharing for discovery
Biomarkers will be essential if research on Parkinson's is to progress, but their discovery depends on scientists sharing data, says Mark Frasier.
- Mark Frasier
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Outlook |
Diagnosis: Warning signs
Non-motor symptoms such as sleep disorders and a poor sense of smell may hold the key to diagnosing Parkinson's disease before the characteristic tremor starts.
- Katherine Bourzac
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Outlook |
Pathology: The prion principle
A controversial theory that could revolutionize our understanding of Parkinson's disease is gaining ground. But not everybody is convinced that misfolded proteins that spread in the brain are the cause of the disease.
- Simon Makin
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Outlook |
Perspective: Finding common ground
Two competing hypotheses about Parkinson's and Gaucher's diseases need to be knitted together, say Anthony H. Futerman and John Hardy.
- Anthony H. Futerman
- & John Hardy
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Article |
Rapid signalling in distinct dopaminergic axons during locomotion and reward
Fast phasic signals in dopaminergic axons in the dorsal striatum occur during, and can induce, motor accelerations in mice, and these signals are transmitted by a largely distinct population of dopaminergic axons from those that signal reward.
- M. W. Howe
- & D. A. Dombeck
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News & Views |
Guilt by genetic association
Certain sequence variants of the α-synuclein gene are linked to the risk of Parkinson's disease. An analysis of these variants using gene-editing technology provides a possible explanation for this increased risk. See Letter p.95
- Asa Abeliovich
- & Herve Rhinn
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News |
Mobile-phone health apps deliver data bounty
Smartphone programs allow researchers to recruit large numbers of participants and monitor them in real time.
- Erika Check Hayden
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News |
Parkinson’s patients trained to respond to placebos
Study suggests how dummy pills might reduce drug doses in routine care.
- Jo Marchant
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News & Views |
Disorder in the court
The native structure of the protein α-synuclein, which is implicated in Parkinson's disease, is controversial. In-cell nuclear magnetic resonance now shows that it remains disordered when loaded into living cells. See Article p.45
- T. Reid Alderson
- & Ad Bax
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News & Views |
Crystals of a toxic core
An ultra-high-resolution structure of the core segment of assembled α-synuclein — the protein that aggregates in the brains of patients with Parkinson's disease — has been determined. A neurobiologist and a structural biologist discuss the implications of this advance. See Article p.486
- Michel Goedert
- & Yifan Cheng
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Article |
Structure of the toxic core of α-synuclein from invisible crystals
A short segment of α-synuclein called NACore (residues 68–78) is responsible for the formation of amyloid aggregates responsible for cytotoxicity in Parkinson disease; here the nanocrystal structure of this invisible-to-optical-microscopy segment is determined using micro-electron diffraction, offering insight into its function and simultaneously demonstrating the first use of micro-electron diffraction to solve a previously unknown protein structure.
- Jose A. Rodriguez
- , Magdalena I. Ivanova
- & David S. Eisenberg
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Article |
The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy
Damaged mitochondria are removed by mitophagy, and defects in mitophagy are linked to Parkinson’s disease; here it is shown that USP30, a deubiquitinase localized to mitochondria, antagonizes mitophagy by removing the ubiquitin tags put in place by Parkin, USP30 inhibition is therefore potentially beneficial for Parkinson’s disease by promoting mitochondrial clearance and quality control.
- Baris Bingol
- , Joy S. Tea
- & Morgan Sheng
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Letter |
Ubiquitin is phosphorylated by PINK1 to activate parkin
Ubiquitin, known for its role in post-translational modification of other proteins, undergoes post-translational modification itself; after a decrease in mitochondrial membrane potential, the kinase enzyme PINK1 phosphorylates ubiquitin at Ser 65, and the phosphorylated ubiquitin then interacts with ubiquitin ligase (E3) enzyme parkin, which is also phosphorylated by PINK1, and this process is sufficient for full activation of parkin enzymatic activity.
- Fumika Koyano
- , Kei Okatsu
- & Noriyuki Matsuda
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Brief Communications Arising |
Properties of native brain α-synuclein
- Jacqueline Burré
- , Sandro Vivona
- & Thomas C. Südhof
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Outlook |
Neurodegeneration: Amyloid awakenings
Sleep disturbances may be an early sign of neurodegenerative diseases — but could sleep deficits cause these conditions in the first place?
- Moheb Costandi
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Research Highlights |
Parkinson's protein spreads
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News |
Misfolded protein transmits Parkinson’s from cell to cell
Link between cell death and protein clumps opens pathway to possible treatment.
- Virginia Hughes
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Letter |
Structural insight into the type-II mitochondrial NADH dehydrogenases
Analysis of the respective crystal structures of the yeast single-component type-II NADH dehydrogenase Ndi1 in its substrate-free form and when bound to NADH, ubiquinone and NADH–ubiquinone shows that Ndi1 homodimerization through its carboxy-terminal domain is critical for its catalytic activity and membrane targeting.
- Yue Feng
- , Wenfei Li
- & Maojun Yang