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Clinical perspective on pluripotent stem cells derived cell therapies for the treatment of neurodegenerative diseases.
Adv Drug Deliv Rev
January 2025
Neurodegenerative Diseases Department, Kadimastem Ltd, Pinchas Sapir 7, Weizmann Science Park, Ness-Ziona, Israel; Department of Molecular Genetics, Weizmann Institute of Science, 76100, Rehovot, Israel.
Self-renewal capacity and potential to differentiate into almost any cell type of the human body makes pluripotent stem cells a valuable starting material for manufacturing of clinical grade cell therapies. Neurodegenerative diseases are characterized by gradual loss of structure or function of neurons, often leading to neuronal death. This results in gradual decline of cognitive, motor, and physiological functions due to the degeneration of the central nervous systems.
View Article and Find Full Text PDFExecutive dysfunction in Parkinson's disease: From neurochemistry to circuits, genetics and neuroimaging.
Prog Neuropsychopharmacol Biol Psychiatry
January 2025
Department of Rehabilitation, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Department of Neurology, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Department of Clinical Medical Research Center, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China. Electronic address:
Cognitive decline is one of the most significant non-motor symptoms of Parkinson's disease (PD), with executive dysfunction (EDF) being the most prominent characteristic of PD-associated cognitive deficits. Currently, lack of uniformity in the conceptualization and assessment scales for executive functions impedes the early and accurate diagnosis of executive dysfunction in PD. The neurobiological mechanisms of executive dysfunction in PD remain poorly understood.
View Article and Find Full Text PDFDynamic Video Assessment of Axial Postural Abnormalities in Parkinson's Disease: A Pilot Study.
Mov Disord Clin Pract
January 2025
Department of Computer Science, University of Verona, Verona, Italy.
Background: Axial postural abnormalities (APAs) are frequent and disabling axial symptoms of Parkinson's disease (PD). Image-based measurement is considered the gold standard but may not accurately detect the true severity of APAs because these symptoms can appear or get worse under dynamic conditions.
Objective: The aim was to evaluate quantitative changes in APAs degree during prolonged standing and walking in both single- and dual-task conditions (motor + cognitive).
aux orchestrates the phosphorylation-dependent assembly of the lysosomal V-ATPase in glia and contributes to SNCA/α-synuclein degradation.
Autophagy
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Glia contribute to the neuropathology of Parkinson disease (PD), but how they react opposingly to be beneficial or detrimental under pathological conditions, like promoting or eliminating SNCA/α-syn (synuclein alpha) inclusions, remains elusive. Here we present evidence that aux (auxilin), the homolog of the PD risk factor GAK (cyclin G associated kinase), regulates the lysosomal degradation of SNCA/α-syn in glia. Lack of glial GAK/aux increases the lysosome number and size, regulates lysosomal acidification and hydrolase activity, and ultimately blocks the degradation of substrates including SNCA/α-syn.
View Article and Find Full Text PDFFunctionally active modulators targeting the LRRK2 WD40 repeat domain identified by FRASE-bot in CACHE Challenge #1.
Chem Sci
January 2025
University of Missouri - Columbia, Department of Chemistry USA
Critical Assessment of Computational Hit-Finding Experiments (CACHE) Challenges emerged as real-life stress tests for computational hit-finding strategies. In CACHE Challenge #1, 23 participants contributed their original workflows to identify small-molecule ligands for the WD40 repeat (WDR) of LRRK2, a promising Parkinson's target. We applied the FRASE-based hit-finding robot (FRASE-bot), a platform for interaction-based screening allowing a drastic reduction of the explorable chemical space and a concurrent detection of putative ligand-binding sites.
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