Documents in Process

Parkinson disease (PD)-associated mutations in the LRRK2 gene hyperactivate LRRK2 kinase activity, leading to increased phosphorylation of a subset of RAB GTPases, which are master regulators of intracellular trafficking. In neurons, processive retrograde transport of autophagosomes is essential for autophagosome maturation and effective degradation of autophagosomal cargo in the axon. [...]

Multiple system atrophy (MSA) and Parkinson's disease (PD) are both α-synucleinopathies with distinct pathological features and disease courses. MSA is characterized by more extensive white matter damage and widespread cortical and subcortical cholinergic systems degeneration than PD. [...]

Body perception and movement control are altered in most neurological, neurodegenerative, and psychiatric diseases. The homuncular organization of the sensorimotor cortex, referring to the regular organization of neurons responsive to body movement and body touch, is therefore of fundamental relevance for brain health. [...]

Protein homeostasis is essential for maintaining normal cellular function. However, protein homeostasis efficiency declines with age, leading to the accumulation of aberrant protein structures associated with neurodegenerative diseases such as Parkinson's disease (PD). [...]

Although α-synuclein pathology is typically associated with Lewy body diseases and multiple systems atrophy, increasing evidence indicates that it also occurs in a group of lysosomal storage disorders termed sphingolipidoses caused by the incomplete degradation, and subsequent accumulation, of a class of lipids termed sphingolipids. Notably, a number of genes that cause sphingolipidoses are also risk genes for Lewy body diseases, suggesting aetiological links between these distinct disorders. [...]

Synucleinopathies are neurodegenerative diseases characterized by the presence of brain inclusions containing the pathologically aggregated protein α-synuclein. The development of a positron emission tomography tracer to detect aggregates of misfolded α-synuclein could revolutionize early diagnosis, disease monitoring, and the evaluation of therapeutic efficacy. [...]

Biologic ventricular assist tissue (BioVAT) is formulated from engineered heart muscle composed of cardiomyocytes and stromal cells derived from allogeneic induced pluripotent stem cells for cardiac remuscularization in patients with heart failure and a reduced left ventricular ejection fraction.We conducted an open-label, phase 1-2 study of tissue-engineered heart repair by means of BioVAT transplantation. Patients with heart failure and a left ventricular ejection fraction of 35% or less and at least one hypokinetic or dyskinetic left ventricular segment were treated with BioVAT allografts, which consisted of 5, 10, or 20 engineered-heart-muscle units. [...]

Overexpression and exogenous administration of the anti-ageing hormone Klotho has been shown to enhance and promote adult hippocampal neurogenesis. However, whether locally produced Klotho from dentate gyrus neurons contributes to this process has remained unclear. [...]

Despite advances in mammography screening, some cancers remain undetected, prompting the evaluation of artificial intelligence (AI) as an independent third reader to reduce missed cancers.In this prospective study, women eligible for the German Mammography Screening were enrolled at six sites belonging to one screening unit between August 2023 and February 2024. Each mammogram underwent double reading and was independently analyzed using Transpara, an AI-based detection software. [...]