Megadalton-sized Dityrosine Aggregates of α-Synuclein Retain High Degrees of Structural Disorder and Internal Dynamics.

Heterogeneous aggregates of the human protein α-synuclein (αSyn) are abundantly found in Lewy body inclusions of Parkinson's disease patients. While structural information on classical αSyn amyloid fibrils is available, little is known about the conformational properties of disease-relevant, non-canonical aggregates. Here, we analyze the structural and dynamic properties of megadalton-sized dityrosine adducts of αSyn that form in the presence of reactive oxygen species and cytochrome c, a proapoptotic peroxidase that is released from mitochondria during sustained oxidative stress.

Molecular imaging insights into neurodegeneration: focus on α-synuclein radiotracers.

Neurodegenerative diseases characterized by the presence of α-synuclein-a hallmark of pathologic inclusions termed Lewy bodies-include Parkinson's disease, dementia with Lewy bodies, and multiple-system atrophy. Although motor symptoms are related to the altered presynaptic dopaminergic function in these diseases, the appearance of α-synuclein inclusions precedes the involvement of the nigrostriatal dopaminergic pathway. Hence, the most accurate and earliest definition of premotor Parkinson's disease ought to rely on imaging α-synuclein rather than dopaminergic changes.

Molecular Imaging Insights into Neurodegeneration: Focus on Tau PET Radiotracers.

Neurodegenerative diseases are characterized by progressive dysfunction and neuronal death, showing specific protein inclusions at autopsy. In vivo detection of these key proteins, namely amyloid-β, tau, α-synuclein, and trans-active response DNA-binding protein 43 kDa, is possible by means of molecular neuroimaging techniques, such as PET. The development of selective PET radiotracers targeting these proteins is critical for early and accurate diagnosis and for the successful development of disease-modifying therapies.

Resolving sentence ambiguity with planning and working memory resources: Evidence from fMRI.

We used functional magnetic resonance imaging (fMRI) to test competing claims about the role of executive resources during the disambiguation of a sentence featuring a temporary structural ambiguity. Written sentences with a direct object (DO) structure or a sentential complement (SC) structure were shown to 19 healthy, right-handed, young adults in a phrase-by-phrase manner. These sentences contained a main verb that is statistically more likely to be associated with a DO structure or an SC structure.