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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

Schweighauser, Shi, Murzin and colleagues report cryo-EM structures of tau filaments from individuals with P301L or P301T MAPT mutations. P301L tau filaments adopted a distinct three-lobed fold, while P301T filaments had either a variant of the three-lobed fold or a V-shaped fold.

Qi et al. used cryo-electron microscopy to determine the structures of tau filaments from the brains of individuals with MAPT mutants V337M and R406W, known to give rise to frontotemporal dementias. They showed that the tau filaments adopted the Alzheimer fold.

A time-resolved cryogenic electron microscopy analysis provides structural information on the processes of primary and secondary nucleation of tau amyloid formation, with implications for the development of new therapies.

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.

Cryo-electron microscopy structures of tau filaments from progressive supranuclear palsy and other tauopathies reveal new filament conformations, and suggest that tauopathies can be classified on several different levels according to their filament folds.

A study using structure determination by cryogenic electron microscopy identifies and characterizes TMEM106B amyloid filaments in human brain, and suggests that their formation is age dependent, with no obvious association with disease.

Cryo-electron microscopy reveals the structures of α-synuclein filaments from the brains of individuals with multiple system atrophy.

Cyro-electron microscopy of tau filaments from people with corticobasal degeneration reveals a previously unseen four-layered fold, distinct from the filament structures seen in Alzheimer’s disease, Pick’s disease and chronic traumatic encephalopathy.

To coincide with the 200th anniversary of the publication of An Essay on the Shaking Palsy by James Parkinson, Goedert and Compston explore the origins of the eponym 'Parkinson's disease'. Although Jean-Martin Charcot is often credited with introducing the name in the 1880s, it can actually be traced back to an 1865 publication by William Rutherford Sanders.

High-resolution structures of tau filaments shed light on the ultrastructure of neurofibrillary lesions in Alzheimer’s disease.

In 1912, Fritz Heinrich Lewy identified the intracellular inclusions that are characteristic of Parkinson disease (PD). Here, Goedert and colleagues present an overview of Lewy's life, including the events leading up to the discovery of the inclusion bodies that now bear his name. They go on to discuss the central role of Lewy pathology in PD and other neurodegenerative disorders, and the research that has elucidated the mechanisms through which α-synuclein aggregation causes neuronal dysfunction and death.

Intracellular tau inclusions, a hallmark of several neurodegenerative diseases, propagate in the brain in an unknown fashion. Brain extracts prepared from mice expressing mutated human tau injected into mice expressing wild-type human tau induce the formation and spread of wild-type human tau inclusions.

The structures of tau filaments from patients with the neurodegenerative disorder Pick’s disease show that the filament fold is different from that of the tau filaments found in Alzheimer’s disease.

Cryo-electron microscopy structures of tau filaments from the brains of three individuals with chronic traumatic encephalopathy reveal distinct assembled tau conformers, with a novel protofilament fold enclosing hydrophobic molecules.

Rodent models are extensively used to investigate the pathophysiology of Alzheimer disease. In this Review, Götz, Bodea and Goedert critically examine the approaches that have been adopted to generate rodent Alzheimer disease models and touch on some of the lessons that have been learned from their use.

A defining characteristic of certain neurodegenerative diseases is the formation of filamentous deposits of a microtubule-associated protein called tau, in an abnormal hyperphosphorylated form. New work shows that this form of tau can bind to a prolyl isomerase called Pin1, and that this interaction restores the biological activity of phosphorylated tau. This discovery could open the way to developing therapeutic compounds that reduce the pool of functionally impaired tau.

Parkinson's disease occurs in a rare familial (inherited) form. At long last researchers have identified a gene which, when mutated, is at least in part responsible for the condition — the mutation changes the amino acid alanine to threonine at a particular position in a protein called a-synuclein. It remains to be seen whether this finding will tell us more about the much more common sporadic form of the disease.

Structural studies of amyloid filaments purified from brains of people with neurodegenerative diseases link specific amyloid folds with distinct diseases and provide a basis for the development of models of neurodegenerative disease.