Cytosolic non-vesicular dopamine accumulation as the predominant mechanism for developing non-DOPA responsive parkinsonism in late-stage Huntington disease

Manalo, Rafael Vincent M.

doi:10.1016/j.mehy.2019.109377

Cited by 3 publications

(4 citation statements)

References 46 publications

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“…accumulation (Manalo 2019), explaining the loss of GFP intensity to the PDE neurons. When co-administered with L-DOPA, the amount of dopamine produced by each PDE neuron may increase, allowing stable dopamine release that may reduce the compensation stress on each neuron (Figure 3(F)).…”

Section: Discussionmentioning

confidence: 98%

“…In contrast, we hypothesise that the lack of efficient caffeine delivery to the tail resulted in aberrant effects that may have been detrimental to the PDE neurons ( Figure 3 ). This resulting subpar tail concentration of caffeine can lead to less protection against oxidative stress, as afforded directly by caffeine, while still activating presynaptic DOP2Rs, which may result to neurodegeneration from cytosolic dopamine accumulation (Manalo 2019 ), explaining the loss of GFP intensity to the PDE neurons. When co-administered with L -DOPA, the amount of dopamine produced by each PDE neuron may increase, allowing stable dopamine release that may reduce the compensation stress on each neuron ( Figure 3(F) ).…”

Section: Discussionmentioning

confidence: 99%

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Caffeine reduces deficits in mechanosensation and locomotion induced by L-DOPA and protects dopaminergic neurons in a transgenic Caenorhabditis elegans model of Parkinson’s disease

Manalo

Medina

2020

Pharmaceutical Biology

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Context: L-DOPA is the first-line drug for Parkinson's disease (PD). However, chronic use can lead to dyskinesia. Caffeine, which is a known neuroprotectant, can potentially act as an adjunct to minimise adverse effects of L-DOPA. Objectives: This study determined changes in terms of neurodegeneration, locomotion and mechanosensation in Caenorhabditis elegans (Rhabditidae) strain UA57 overexpressing tyrosine hydroxylase (CAT-2) when treated with caffeine, L-DOPA or their combinations. Materials and methods: Neurodegeneration was monitored via fluorescence microscopy of GFP-tagged dopaminergic neurons in the head and tail regions of C. elegans. Meanwhile, mechanosensation and locomotion under vehicle (0.1% DMSO), L-DOPA (60 mM), caffeine (10 mM) or 60 mM L-DOPA þ 10 or 20 mM caffeine (60LC10 and 60LC20) treatments were scored for 3 days (n ¼ 20). Results: L-DOPA (60 mM) reduced CEP and ADE neurons by 4.3% on day 3, with a concomitant decrease in fluorescence by 44.6%. This correlated with reductions in gentle head (À35%) and nose touch (À40%) responses, but improved locomotion (20-75%) compared with vehicle alone. CEP and ADE neuron counts were preserved with caffeine (10 mM) or 60LC10 (98-100%), which correlated with improved mechanosensation (10-23%) and locomotion (18-76%). However, none of the treatments was able to preserve PDE neuron count, reducing the basal slowing response. Discussion and conclusions: Taken together, we show that caffeine can protect DAergic neurons and can reduce aberrant locomotion and loss of sensation when co-administered with L-DOPA, which can potentially impact PD treatment and warrants further investigation.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Caffeine reduces deficits in mechanosensation and locomotion induced by L-DOPA and protects dopaminergic neurons in a transgenic Caenorhabditis elegans model of Parkinson’s disease

Manalo

Medina

2020

Pharmaceutical Biology

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“…[1][2][3][4] It has been evidenced that the excessive secretion of DA can lead to palpitations, dyspnea, chest pain, arrhythmia and general weakness, and even death in severe cases. [5][6][7] Differently, lack of DA makes muscle out of control, leading to aprosexia and even Parkinson's disease. [8,9] Therefore, the determination of DA content is of significant importance for the understanding and diagnosis of these neurological diseases.…”

Section: Introductionmentioning

confidence: 99%

Organic Molecule Modified Phosphotungstate with Helical Structure for Electrochemical Detection of Dopamine

Liu

Zhang

Yang

et al. 2020

Zeitschrift anorg allge chemie

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To overcome the water solubility and aggregation of heteropoly acids (HPAs), and to promote its application in the electrochemical biosensors, organic molecular modification strategy was employed by simple hydrothermal synthesis. Herein, an unprecedented phosphotungstate (PTA)‐based three‐dimensional supramolecular framework with helical structure, [(bix)2(H3PW12O40)·H2O] [PTA‐bix, bix = 1,3‐bis(imidazol‐1‐ylmethyl) benzene], was synthesized and characterized. And the PTA‐bix modified glassy carbon electrode shows the high sensitivity and catalytic activity for detecting the neurotransmitter dopamine (DA) with the linear detection range from 1 μM to 100 μM, and the detection limit of differential pulse voltammetry (DPV) is 0.85 μM. The concept behinds the new architecture to modify electrodes should promote the further development of HPA hybrid crystal material‐based biosensors.

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“…However, diseased neurons have a reduced number of synaptic vesicles with lower concentrations of neurotransmitters, and therefore causing decreased levels to reach out to the postsynaptic receptors, leading to lack of signal processing and neurological disorders. Even minor fluctuations of dopamine at these receptors have been related to systematic dysfunctions along with the possible onset of neurodegenerative diseases such as with Parkinson's disease, [8][9][10][11] Schizophrenia, [12][13][14] and Huntington's Disease. 15,16 Dopamine is generated mainly within the striatum, more specifically at the substantia nigra, ventral tegmental area, and hypothalamus, 17 where accessibility and measurements in these areas are difficult and require invasive procedures.…”

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confidence: 99%

Review—Catalytic Electrochemical Biosensors for Dopamine: Design, Performance, and Healthcare Applications

DeVoe,

Andreescu

2024

ECS Sens. Plus

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The effect of an Al2TiO5 (ALT) interlayer between Ni and YSZ on enhancing the thermal stability of Ni-YSZ solid oxide fuel cell was examined. Atomic layer deposition (ALD) was used to provide precise control of the structure and thickness of the ALT interlayer. The study’s findings demonstrate that a 2 nm thick ALT interlayer deposited by ALD does not adversely affect the cell’s ohmic resistance and effectively prevents Ni sintering and the loss of active area during high-temperature heat treatments. ALT layers thicker than 2 nm, although they enhanced Ni stability, were found to impede oxygen ion transport in the electrode and significantly increase the ohmic resistance of the cell, leading to a decline in performance.

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Cytosolic non-vesicular dopamine accumulation as the predominant mechanism for developing non-DOPA responsive parkinsonism in late-stage Huntington disease

Cited by 3 publications

References 46 publications

Caffeine reduces deficits in mechanosensation and locomotion induced by L-DOPA and protects dopaminergic neurons in a transgenic Caenorhabditis elegans model of Parkinson’s disease

Caffeine reduces deficits in mechanosensation and locomotion induced by L-DOPA and protects dopaminergic neurons in a transgenic Caenorhabditis elegans model of Parkinson’s disease

Organic Molecule Modified Phosphotungstate with Helical Structure for Electrochemical Detection of Dopamine

Review—Catalytic Electrochemical Biosensors for Dopamine: Design, Performance, and Healthcare Applications

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