Regulation of tyrosine hydroxylase: relevance to Parkinson's disease

Alam, Gelareh; Richardson, Jason

doi:10.1016/b978-0-12-815950-7.00004-7

Cited by 9 publications

(11 citation statements)

References 36 publications

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“…The loss of TH and synuclein accumulation has been reported as a major cause of PD progression. Thus, TH recovery and synuclein inhibition pave the way for PD treatment . The result has shown ∼10 fold reduction in the TH expression and the FCsnps exhibited ∼20 fold improvement in the TH expression.…”

Section: Resultsmentioning

confidence: 94%

FTY720 Nanoformulation Induces O-GlcNacylation of Synuclein to Alleviate Synucleinopathy

Sardoiwala,

Boddu,

Biswal

et al. 2023

ACS Chem. Neurosci.

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The post-translational modification and aggregation of alpha-synuclein are one of the major causes of Parkinson's disease (PD) regulation. In that, the phosphorylation and nitration of synuclein elevate the aggregation, while O-GlcNacylation prevents the aggregation of synuclein. The inhibition of synuclein aggregation directs the development of PD therapy. The endowed O-GlcNacylation of synuclein could be a promising strategy to inhibit synucleinopathy. Therefore, the neuroprotective chitosanbased FTY720 nanoformulation, PP2A (Protein phosphatase 2) activator has been employed to evaluate the PP2A role in the O-GlcNacylation of synuclein in an in vivo PD model. The neuroprotective effect of our nanoformulation is attributed to the upregulation of tyrosine hydroxylase (TH), the PD therapeutic target, with behavioral improvement in animals against rotenone-induced PD deficits. The neuroprotective molecular insights revealed the camouflaged role of PP2A by endowing the OGT activity that induces O-GlcNacylation of synuclein in the reduction of synucleinopathy.

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Section: Resultsmentioning

confidence: 94%

FTY720 Nanoformulation Induces O-GlcNacylation of Synuclein to Alleviate Synucleinopathy

Sardoiwala,

Boddu,

Biswal

et al. 2023

ACS Chem. Neurosci.

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“…Broadly, dopamine terminals can be separated in presynaptic and postsynaptic terminals. At the presynaptic level, tyrosine hydroxylase (TH), a rate‐limiting enzyme involved in the biosynthesis of catecholamines (Haavik & Toska, 1998), converts l ‐Tyrosine into 3,4‐dihydroxyphenylalanine ( l ‐Dopa) (Alam & Richardson, 2020). TH is also used as a post‐mortem immunochemistry marker for neuromelanin‐positive dopaminergic cells in the SN (Kraemmer et al, 2014).…”

Section: Functional Dopaminergic Imagingmentioning

confidence: 99%

Dopaminergic imaging in degenerative parkinsonisms, an established clinical diagnostic tool

Nicastro

Nencha

Burkhard

et al. 2022

Journal of Neurochemistry

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Parkinson's disease (PD) and other neurodegenerative parkinsonisms are characterised by loss of striatal dopaminergic neurons. Dopamine functional deficits can be measured in vivo using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) ligands assessing either presynaptic (e.g. dopamine synthesis and storage, transporter density) or postsynaptic terminals (i.e. D2 receptors availability). Nuclear medicine imaging thus helps the clinician to separate degenerative forms of parkinsonism with other neurological conditions, e.g. essential tremor or drug-induced parkinsonism. With the present study, we aimed at summarizing the current evidence about dopaminergic molecular imaging in the diagnostic evaluation of PD, atypical parkinsonian syndromes and dementia with Lewy bodies (DLB), as well as its potential to distinguish these conditions and to estimate disease progression. In fact, PET/SPECT methods are clinically validated and have been increasingly integrated into diagnostic guidelines (e.g. for PD and DLB). In addition, there is novel evidence on the classification properties of extrastriatal signal. Finally, dopamine imaging has an outstanding potential to detect neurodegeneration at the premotor stage, including REM-sleep behavior disorder and olfactory loss. Therefore, inclusion of subjects at an early stage for clinical trials can largely benefit from a validated in vivo biomarker such as presynaptic dopamine pathways PET/SPECT assessment.

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“…TH and TUBB-3 are good target genes to understand the health and functionality of neural cells; TH encodes for the rate-limiting enzyme tyrosine hydroxylase, which converts tyrosine during the creation of catecholamines, including dopamine. 26,27 TUBB-3 is involved with multiple aspects of cell health and behavior, including forming the cytoskeleton and neurogenesis. 28,29 Analyzing the expression of these genes can give vital cues as to how dopaminergic neural N27 cells are behaving 1 day after manufacturing in hollow alginate microfibers, which is a key factor to designing BBB models that allow for efficient and accurate modeling of BBB.…”

mentioning

confidence: 99%

“…To better understand the genetic implications of the manufacturing process and encapsulating cells into 3D tubular structures, reverse-transcription (RT) quantitative polymerase chain reactions (qPCR) were used to analyze the gene expressions of tyrosine hydroxylase (TH) and tubulin beta 3 class III (TUBB-3) relative to the endogenous control beta-2 microglobulin (B2M). TH and TUBB-3 are good target genes to understand the health and functionality of neural cells; TH encodes for the rate-limiting enzyme tyrosine hydroxylase, which converts tyrosine during the creation of catecholamines, including dopamine. , TUBB-3 is involved with multiple aspects of cell health and behavior, including forming the cytoskeleton and neurogenesis. , Analyzing the expression of these genes can give vital cues as to how dopaminergic neural N27 cells are behaving 1 day after manufacturing in hollow alginate microfibers, which is a key factor to designing BBB models that allow for efficient and accurate modeling of BBB.…”

mentioning

confidence: 99%

Targeted Microfluidic Manufacturing to Mimic Biological Microenvironments: Cell-Encapsulated Hollow Fibers

et al. 2021

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At present, the blood-brain barrier (BBB) poses a challenge for treating a wide range of central nervous system disorders; reliable BBB models are still needed to understand and manipulate the transfer of molecules into the brain, thereby improving the efficiency of treatments. In this study, hollow, cell-laden microfibers are fabricated and investigated as a starting point for generating BBB models. The genetic effects of the manufacturing process are analyzed to understand the implications of encapsulating cells in this manner. These fibers are created using different manufacturing parameters to understand the effects on wall thickness and overall diameter. Then, dopaminergic rat cells are encapsulated into hollow fibers, which maintained at least 60% live cells throughout the three-day observation period. Lastly, genetic changes TH and TUBB-3 are investigated to elucidate the effects on cell health and behavior; while the TH levels in encapsulated cells were similar to control cells, showing similar levels of tyrosine hydroxylase synthesis, TUBB-3 was downregulated, indicating lower amounts of cellular neurogenesis.As the national and international population continues to grow older, age-related neuropathologies continue to be a tragic and expensive bane of modern times, with Alzheimer's alone projected to cost 1.1 trillion dollars per year by 2050, 1 while general neurological disorders account for 12% of the total global deaths. 2 Similarly, there is a dire need to treat other neurological disorders, such as mental illnesses, cancers, or traumatic brain injuries (TBIs), which are widespread and are detrimental to a wide age range. [3][4] In spite of this urgency, a currently insurmountable challenge has blocked efforts thus far; while it is crucial to protect the integrity of the central nervous system (CNS), the blood-brain barrier (BBB) blocks more than 98% of small molecules and all large molecules, thwarting almost all efforts to provide therapeutics to the brain. 5 Creating physiologically relevant BBB models is a crucial step to providing care for millions of patients across the globe, as it will allow for the rapid and reliable creation of effective neuropharmacological molecules.

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Regulation of tyrosine hydroxylase: relevance to Parkinson's disease

Cited by 9 publications

References 36 publications

FTY720 Nanoformulation Induces O-GlcNacylation of Synuclein to Alleviate Synucleinopathy

FTY720 Nanoformulation Induces O-GlcNacylation of Synuclein to Alleviate Synucleinopathy

Dopaminergic imaging in degenerative parkinsonisms, an established clinical diagnostic tool

Targeted Microfluidic Manufacturing to Mimic Biological Microenvironments: Cell-Encapsulated Hollow Fibers

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