Alterations in lysosomal and proteasomal markers in Parkinson's disease: relationship to alpha-synuclein inclusions

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Amyotrophic lateral sclerosis (ALS) with only motor impairment (ALS-pure motor) and the behavioral variant of frontotemporal dementia (bvFTD) are hypothesized to represent extreme ends of a disease spectrum, which encompasses ALS with cognitive/behavioral ...

Neurodegenerative diseases (NDDs), such as Parkinson's disease and Alzheimer's disease present a significant global health concern. The misfolding of proteins from native disordered monomeric forms into beta-sheet enriched aggregates of oligomers and fibri ...

Hemispheric asymmetry is a universal property of brain organization with wide implications into brain function and structure, and diseases. This study presents a laterality index for characterizing hemispheric asymmetries that underlie cortical maps using ...

Amyloid-forming proteins such alpha-synuclein and tau, which are implicated in Alzheimer's and Parkinson's disease, can form different fibril structures or strains with distinct toxic properties, seeding activities and pathology. Understanding the determin ...

Neuropathological tau tangles in Alzerheimer’s disease (AD) have been roughly characterized into pre‐tangles, mature tangles and ghost tangles. However, to date, their maturation in the human brain is poorly understood. Here, we aimed to define the structu ...

Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2 ' 3 '-cyclic GMP-AMP (cGAMP)1-7. The indiscriminate activity of cGAS towards DNA d ...

Multiple System Atrophy is characterized pathologically by the accumulation of alpha-synuclein (aSyn) into glial cytoplasmic inclusions (GCIs). The mechanism underlying the formation of GCIs is not well understood. In this study, correlative light and elec ...

The application of computational biology in drug development for membrane protein targets has experienced a boost from recent developments in deep learning-driven structure prediction, increased speed and resolution of structure elucidation, machine learni ...

DNA damage signaling following DNA double-strand breaks (DSBs) involves numerous regulating proteins, which dynamically recognize ('read') and alter ('write' or 'erase') histone post-translational modifications (PTMs). Among these PTMs, the ubiquitin syste ...

Huntington's disease (HD) is a devastating neurodegenerative disorder marked by the accumulation of Huntingtin protein (HTT) fragments in HD neuronal cells. These aggregates are predominantly composed of polyglutamine (polyQ)-containing HTT N-terminal frag ...

Post-translational modifications (PTMs) play a pivotal role in regulating protein structure, interaction, and function. Aberrant PTM patterns are associated with diseases. Moreover, individual PTMs have a complex interaction with each other, known as PTM c ...

Atomic force microscopy (AFM) is a widely used imaging tool for obtaining a variety of information for a range of samples. Although it was initially intended to serve as a method of observing very flat solid surfaces, its use expanded into several other fi ...

Background and objectives Neuropsychiatric symptoms (NPS) are common in older people with cognitive impairment and Alzheimer's disease (AD). No biomarkers to detect the related pathology or predict the clinical evolution of NPS are available yet. This stud ...

Although it has been nearly two and half decades since the discovery of alpha-synuclein (aSyn) as the major component of Lewy bodies (LBs), our understanding of the involvement of different aSyn species, their seeding, spreading and toxicity in Parkinson's ...

Aggregated alpha-synuclein (alpha-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA ...

Background Braak's hypothesis states that sporadic Parkinson's disease (PD) follows a specific progression of pathology from the peripheral to the central nervous system, and this progression can be monitored by detecting the accumulation of alpha-Synuclei ...

Antibodies against phosphorylated alpha-synuclein (aSyn) at 5129 have emerged as the primary tools to investigate, monitor, and quantify aSyn pathology in the brain and peripheral tissues of patients with Parkinson's disease and other neurodegenerative dis ...

Alpha-synuclein (aSyn) is a pre-synaptic monomeric protein that can form aggregates in neurons in Parkinson's disease (PD), Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB), and in oligodendrocytes in multiple system atrophy (MSA ...

The cellular protein levels are determined by protein synthesis and turnover rates. Two processes are involved in the proteome's turnover in proliferating cells: protein degradation and dilution. In theory, maintaining the cellular proteome concentration, ...

The abnormal aggregation and accumulation of alpha-synuclein (aSyn) in the brain is a defining hallmark of synucleinopathies. Various aSyn conformations and post-translationally modified forms accumulate in pathological inclusions and vary in abundance amo ...

Alterations in lysosomal and proteasomal markers in Parkinson's disease: relationship to alpha-synuclein inclusions

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Longitudinal changes in MEG-based brain network topology of ALS patients with cognitive/behavioral impairment—An exploratory study

Nanoplasmonic infrared biosensors enabling detection of misfolded protein biomarkers and drug screening for neurodegenerative diseases

Multiscale Quantification of Hemispheric Asymmetry in Cortical Maps Using Geometric Eigenmodes

O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology

Ultrastructural characterization of tau pathology in the human post‐mortem Alzheimer’s disease brain

The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation

Distinct ultrastructural phenotypes of glial and neuronal alpha-synuclein inclusions in multiple system atrophy

Computational drug development for membrane protein targets

A chemical biology approach to decipher chromatin ubiquitylation by RNF168

Exploring the therapeutic potential of Huntingtin native state stabilization through targeting its interacting partners

Investigating the intra-molecular and inter-molecular effects of post-translational modifications on intrinsically disordered protein regions and structured protein regions

Advancements in Nanomechanical Characterization and Biomolecular Imaging with Atomic force Microscopy

Neuropsychiatric symptoms in cognitive decline and Alzheimer's disease: biomarker discovery using plasma proteomics

Towards elucidating the structural and cellular determinants of a-synuclein seeding and toxicity

Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson's Disease and Multiple System Atrophy

Overexpression of human alpha-Synuclein leads to dysregulated microbiome/metabolites with ageing in a rat model of Parkinson disease

Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity

Prominent astrocytic alpha-synuclein pathology with unique post-translational modification signatures unveiled across Lewy body disorders

Coordination of protein synthesis and degradation in mammalian cells

Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases