506 results match your criteria: "Translational Neurodegeneration[Journal]"

Background: Alzheimer's disease (AD) is the most common form of neurodegenerative disorder, which is characterized by a decline in cognitive abilities. Genome-wide association and clinicopathological studies have demonstrated that the CD2-associated protein (CD2AP) gene is one of the most important genetic risk factors for AD. However, the precise mechanisms by which CD2AP is linked to AD pathogenesis remain unclear.

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Astrocytes contribute to toll-like receptor 2-mediated neurodegeneration and alpha-synuclein pathology in a human midbrain Parkinson's model.

Transl Neurodegener

December 2024

School of Medical Sciences, Faculty of Medicine and Health and the Brain and Mind Centre, University of Sydney, Camperdown, NSW, 2050, Australia.

Background: Parkinson's disease (PD) is characterised by degeneration of ventral midbrain dopaminergic (DA) neurons and abnormal deposition of α-synuclein (α-syn) in neurons. Activation of the innate immune pathogen recognition receptor toll-like receptor 2 (TLR2) is associated with exacerbation of α-syn pathology. TLR2 is increased on neurons in the PD brain, and its activation results in the accumulation and propagation of α-syn through autophagy inhibition in neurons.

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Extracellular vesicles: biological mechanisms and emerging therapeutic opportunities in neurodegenerative diseases.

Transl Neurodegener

December 2024

The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.

Article Synopsis
  • Extracellular vesicles (EVs) are membrane-bound structures released by brain cells, playing an increasingly recognized role in neurodegenerative diseases.
  • Research has shifted from basic biology of EVs to their clinical applications, particularly in identifying biomarkers and therapeutic targets for these diseases.
  • The review discusses the characteristics, functions, and biological mechanisms of different types of brain-derived EVs, along with potential therapeutic strategies and challenges in using EVs for drug delivery.
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  • Researchers are investigating new ways to replace or regenerate lost neurons in neurodegenerative diseases, specifically through direct reprogramming of astrocytes into neurons by manipulating a protein called PTBP1.
  • Some studies claim that this reprogramming leads to functional neurons and better disease outcomes in animal models, while others challenge these findings, questioning the effectiveness of PTBP1 suppression for this purpose.
  • The review highlights recent advancements in regenerative treatments like stem cell transplants for conditions such as Parkinson's and Alzheimer's, suggesting that differences in astrocyte types may explain the mixed results in research regarding their conversion to neurons.*
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Aquaporin-4 as a cerebrospinal fluid biomarker of Alzheimer's disease.

Transl Neurodegener

November 2024

Department of Neurology, University Clinic, University Hospital Halle, Martin Luther University, Ernst-Grube Strasse 40, 06120, Halle (Saale), Germany.

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The spectrum of synucleinopathies, including Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), is characterized by α-synuclein (αSyn) pathology, which serves as the definitive diagnostic marker. However, current diagnostic methods primarily rely on motor symptoms that manifest years after the initial neuropathological changes, thereby delaying potential treatment. The symptomatic overlap between PD and MSA further complicates the diagnosis, highlighting the need for precise and differential diagnostic methods for these overlapping neurodegenerative diseases.

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Cellular senescence in Alzheimer's disease: from physiology to pathology.

Transl Neurodegener

November 2024

Laboratory of Exercise and Neurobiology, School of Physical Education and Sports Science, South China Normal University, Guangzhou, 510006, Guangdong, China.

Article Synopsis
  • Alzheimer's disease (AD) involves the buildup of Aβ proteins and tau hyperphosphorylation, but effective treatments remain scarce despite drug development efforts.
  • There is growing interest in the role of cellular senescence in AD progression, with evidence indicating that targeting senescence could improve cognitive function and reduce AD symptoms.
  • The review covers the characteristics and biomarkers of cellular senescence, explores various brain cell types involved, and highlights potential treatments like senolytics and senomorphics as promising strategies for managing AD.
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  • Increased levels of ROCK1 in the brains of Alzheimer's disease (AD) patients correlate positively with lysosomal dysfunction and Aβ accumulation, suggesting its role in AD pathogenesis.
  • The study demonstrates that knocking down ROCK1 enhances lysosomal function and promotes the clearance of Aβ by facilitating TFEB's nuclear distribution.
  • Targeting ROCK1 may provide a potential therapeutic strategy to restore lysosomal homeostasis and mitigate cognitive decline in AD models.*
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A tumorigenicity evaluation platform for cell therapies based on brain organoids.

Transl Neurodegener

October 2024

Department of Neurosurgery, Huashan Hospital, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200040, China.

Article Synopsis
  • Tumorigenicity in stem cell therapies poses significant challenges, prompting the need for improved evaluation methods beyond conventional animal models; brain organoids mimic human brain structure but require further exploration for tumorigenicity assessment.
  • A study utilized a cerebral organoid model derived from human pluripotent stem cells and a glioblastoma-like organoid to enhance sensitivity in detecting tumorigenic cells, comparing injected neuronal cells in both organoid types and mice.
  • Results indicated that glioblastoma organoids significantly increased the proliferation and pluripotency of injected human pluripotent stem cells compared to cerebral organoids and in vivo models, showcasing their potential as a better platform for tumorigenicity evaluation.
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Background: Persistent innate and adaptive immune responses in the brain contribute to the progression of Alzheimer's disease (AD). APOE4, the most important genetic risk factor for sporadic AD, encodes apolipoprotein E4, which by itself is a potent modulator of immune response. However, little is known about the immune hub that governs the crosstalk between the nervous and the adaptive immune systems.

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  • Therapeutic strategies to lower mutant huntingtin (mHTT) levels show promise in reversing Huntington's disease (HD) symptoms in animal models, highlighting the need for effective biomarkers to evaluate these therapies.
  • Neurofilament light chain (NfL) is a neurodegeneration biomarker that increases in the cerebrospinal fluid (CSF) and blood as HD progresses, but its role in assessing treatment efficacy remains unclear.
  • In studies with YAC128 mice, NfL levels were elevated compared to control mice, and while lowering mHTT before disease symptoms had minimal impact on plasma NfL, it led to a significant reduction in CSF NfL, especially when treatment was started after disease onset.
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Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson's disease.

Transl Neurodegener

September 2024

Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China.

Parkinson's disease (PD) is the second most common neurodegenerative disease. The development of PD is closely linked to genetic and environmental factors, with GBA1 variants being the most common genetic risk. Mutations in the GBA1 gene lead to reduced activity of the coded enzyme, glucocerebrosidase, which mediates the development of PD by affecting lipid metabolism (especially sphingolipids), lysosomal autophagy, endoplasmic reticulum, as well as mitochondrial and other cellular functions.

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Neurodegenerative diseases are associated with chronic neuroinflammation in the brain, which can result in microglial phagocytosis of live synapses and neurons that may contribute to cognitive deficits and neuronal loss. The microglial P2Y receptor (P2YR) is a G-protein coupled receptor, which stimulates microglial phagocytosis when activated by extracellular uridine diphosphate, released by stressed neurons. Knockout or inhibition of P2YR can prevent neuronal loss in mouse models of Alzheimer's disease (AD), Parkinson's disease, epilepsy, neuroinflammation and aging, and prevent cognitive deficits in models of AD, epilepsy and aging.

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Neurodegenerative disorders, metabolic icebergs, and mitohormesis.

Transl Neurodegener

September 2024

Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, 10032, USA.

Neurodegenerative disorders are typically "split" based on their hallmark clinical, anatomical, and pathological features, but they can also be "lumped" by a shared feature of impaired mitochondrial biology. This leads us to present a scientific framework that conceptualizes Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) as "metabolic icebergs" comprised of a tip, a bulk, and a base. The visible tip conveys the hallmark neurological symptoms, neurodegenerative regions, and neuronal protein aggregates for each disorder.

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Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized pathologically by extracellular deposition of β-amyloid (Aβ) into senile plaques and intracellular accumulation of hyperphosphorylated tau (pTau) as neurofibrillary tangles. Clinically, AD patients show memory deterioration with varying cognitive dysfunctions. The exact molecular mechanisms underlying AD are still not fully understood, and there are no efficient drugs to stop or reverse the disease progression.

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Article Synopsis
  • Diagnosing neurodegenerative diseases (NDDs) is difficult and current therapies are not very effective, but using nanostructures can enhance drug delivery and theranostics.
  • *Hybrid nanostructures, created by combining different types of nanomaterials, offer benefits such as better targeting, biocompatibility, and controlled drug release for treating NDDs.
  • *The paper reviews recent advances in hybrid nanostructures, discusses engineering techniques for their creation, and considers challenges and future possibilities in translating these techniques into therapies for NDDs.*
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Alzheimer's disease (AD) is a progressive neurological disorder that primarily impacts cognitive function. Currently there are no disease-modifying treatments to stop or slow its progression. Recent studies have found that several peripheral and systemic abnormalities are associated with AD, and our understanding of how these alterations contribute to AD is becoming more apparent.

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The rising prevalence of diabetes mellitus has casted a spotlight on one of its significant sequelae: cognitive impairment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for diabetes management, are increasingly studied for their cognitive benefits. These benefits may include reduction of oxidative stress and neuroinflammation, decrease of amyloid burdens, enhancement of neuronal plasticity, and improved cerebral glucose utilization.

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Tau in neurodegenerative diseases: molecular mechanisms, biomarkers, and therapeutic strategies.

Transl Neurodegener

August 2024

Faculty of Life and Health Sciences, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.

The deposition of abnormal tau protein is characteristic of Alzheimer's disease (AD) and a class of neurodegenerative diseases called tauopathies. Physiologically, tau maintains an intrinsically disordered structure and plays diverse roles in neurons. Pathologically, tau undergoes abnormal post-translational modifications and forms oligomers or fibrous aggregates in tauopathies.

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