Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson’s disease

Translational Neurodegeneration, Год журнала: 2024, Номер 13(1)

Опубликована: Сен. 12, 2024

Язык: Английский

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Increased glucosylsphingosine levels and Gaucher Disease in GBA1-associated Parkinson’s Disease.

Parkinsonism & Related Disorders, Год журнала: 2024, Номер 124, С. 107023 - 107023

Опубликована: Июнь 1, 2024

Язык: Английский

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What We Know About TMEM175 in Parkinson's Disease

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(1)

Опубликована: Янв. 1, 2025

ABSTRACT Background Lysosome is a highly heterogeneous membranous organelle in eukaryotic cells, which regulates many physiological processes the cell. Studies have found that lysosomal dysfunction disrupts cellular homeostasis and associated with Parkinson's disease (PD). Transmembrane protein 175 (TMEM175) cation channel whose activity essential for homeostasis. At present, it has been confirmed TMEM175 related to pathogenesis of PD, but relationship between two remains unclear. Aims A thorough comprehension structure function would greatly contribute elucidating achievement this objective. In paper, structure, composition, its PD will be reviewed.

Язык: Английский

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α-Synuclein pathology and mitochondrial dysfunction: Toxic partners in Parkinson's disease

Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106889 - 106889

Опубликована: Март 1, 2025

Two major neuropathological features of Parkinson's disease (PD) are α-synuclein Lewy pathology and mitochondrial dysfunction. Although both dysfunction may independently contribute to PD pathogenesis, the interaction between these two factors is not yet fully understood. In this review, we discuss physiological functions homeostasis in neurons as well pathological defects that ensue when disturbed PD. Recent studies have highlighted dysfunctional mitochondria can become sequestered within bodies, cell biology suggested directly impair function. There also cases caused by genetic or environmental perturbation homeostasis. Together, suggest be a common pathway neurodegeneration PD, triggered multiple insults. We review literature surrounding highlight open questions field explored advance our understanding develop novel, disease-modifying therapies.

Язык: Английский

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Mechanism and therapeutic targets of the involvement of a novel lysosomal proton channel TMEM175 in Parkinson's disease

Ageing Research Reviews, Год журнала: 2024, Номер 100, С. 102373 - 102373

Опубликована: Июль 2, 2024

Язык: Английский

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Emerging Molecular‐Genetic Families in Dystonia: Endosome‐Autophagosome‐Lysosome and Integrated Stress Response Pathways

Movement Disorders, Год журнала: 2024, Номер unknown

Опубликована: Окт. 28, 2024

Abstract Advances in genetic technologies and disease modeling have greatly accelerated the pace of introducing validating molecular‐genetic contributors to disease. In dystonia, there is a growing convergence across multiple distinct forms onto core biological processes. Here, we discuss two these, endosome‐autophagosome‐lysosome pathway integrated stress response, highlight recent advances field. Using these pathomechanisms as examples, further opportunities that grouping dystonias present transform dystonia care. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf International Parkinson Disorder Society.

Язык: Английский

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Rotenone Blocks the Glucocerebrosidase Enzyme and Induces the Accumulation of Lysosomes and Autophagolysosomes Independently of LRRK2 Kinase in HEK-293 Cells

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(13), С. 10589 - 10589

Опубликована: Июнь 24, 2023

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the progressive loss of dopaminergic (DAergic) neurons in substantia nigra and intraneuronal presence Lewy bodies (LBs), composed aggregates phosphorylated alpha-synuclein at residue Ser129 (p-Ser129α-Syn). Unfortunately, no curative treatment available yet. To aggravate matters further, etiopathogenesis still unresolved. However, neurotoxin rotenone (ROT) has been implicated PD. Therefore, it widely used to understand molecular mechanism neuronal cell death. In present investigation, we show that ROT induces two convergent pathways HEK-293 cells. First, generates H2O2, which, turn, either oxidizes stress sensor protein DJ-Cys106-SH into DJ-1Cys106SO3 or phosphorylation LRRK2 kinase Ser395 (p-Ser395 LRRK2). Once active, phosphorylates α-Syn (at Ser129), mitochondrial membrane potential (ΔΨm), triggers production cleaved caspase 3 (CC3), resulting signs apoptotic also reduces glucocerebrosidase (GCase) activity concomitant with accumulation lysosomes autophagolysosomes reflected increase LC3-II (microtubule-associated 1A/1B-light chain 3-phosphatidylethanolamine conjugate II) markers Second, exposure knockout (KO) cells displays an almost-normal phenotype. Indeed, KO showed neither DJ-1Cys106SO3, p-Ser395 LRRK2, p-Ser129α-Syn, nor CC3 but displayed high ΔΨm, reduced GCase activity, autophagolysosomes. Similar observations are obtained when wild-type (WT) exposed inhibitor conduritol-β-epoxide (CBE). Taken together, these imply combined development inhibitors compounds for recovering might be promising therapeutic agents

Язык: Английский

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Comprehensive Analysis and Experimental Validation of the Parkinson’s Disease Lysosomal Gene ACP2 and Pan-cancer

Biochemical Genetics, Год журнала: 2024, Номер unknown

Опубликована: Фев. 3, 2024

Язык: Английский

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Social Cognitive Rehabilitation for Neurodegenerative Disorders

Advances in medical technologies and clinical practice book series, Год журнала: 2024, Номер unknown, С. 269 - 287

Опубликована: Март 22, 2024

In this chapter, an initial exploration of the definition and symptoms neurodegenerative disorders will be conducted along with in-depth analysis their underlying neurobiological basis, shedding light on manifestation in brain. The central focus then shift towards comprehending addressing specific social cognitive deficits associated different types NDs examining challenges posed realm cognition. Strategies interventions specifically designed for rehabilitation investigated. chapter encompass a discussion caregiver burden effective coping strategies to alleviate stresses faced. primary objective is provide readers comprehensive understanding intricate nature equip them practical tools aimed at enhancing cognition improving quality life individuals affected by these complex conditions.

Язык: Английский

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Exploring the triad: VPS35, neurogenesis, and neurodegenerative diseases

Journal of Neurochemistry, Год журнала: 2024, Номер unknown

Опубликована: Июль 18, 2024

Abstract Vacuolar protein sorting 35 (VPS35), a critical component of the retromer complex, plays pivotal role in pathogenesis neurodegenerative diseases (NDs). It is involved transmembrane sorting, facilitating transport from endosomes to trans‐Golgi network (TGN) and plasma membrane. Recent investigations have compellingly associated mutations VPS35 gene with disorders such as Parkinson's Alzheimer's disease. These genetic alterations are implicated misfolding, disrupted autophagic processes, mitochondrial dysregulation, synaptic impairment. Furthermore, exerts notable impact on neurogenesis by influencing neuronal functionality, conveyance, performance. Dysregulation or mutation may escalate progression conditions, underscoring its safeguarding integrity. This review comprehensively discusses functional impairments NDs. we provide an overview further explore intricate relationship between research advancements offer novel perspectives valuable insights for identifying potential therapeutic targets treatment image

Язык: Английский

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