FTY720 Nanoformulation Induces O-GlcNacylation of Synuclein to Alleviate Synucleinopathy

Sardoiwala, Mohammed Nadim; Boddu, Mrunalini; Biswal, Liku; Karmakar, Surajit; Choudhury, Subhasree Roy

doi:10.1021/acschemneuro.3c00545

Cited by 3 publications

(2 citation statements)

References 32 publications

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“…IP study conducted to explore physical interaction of desired protein markers by following the existing protocol . Equal amounts of protein samples were incubated for 1 h with 20 μL of agarose (A/G) beads (SCBT, USA) at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

Hytrin Nanoformulation Reduces Nitrated Synucleinopathy Through Chaperon-Mediated Autophagy

Sardoiwala,

Boddu,

Biswal

et al. 2024

ACS Appl. Nano Mater.

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The loss of dopaminergic neurons, majorly due to synucleinopathy, is the prime cause of Parkinson's disease (PD) progression. Like phosphorylated synuclein, nitrated synuclein also significantly contributes to Lewy body formation in the PD etiology. Therefore, an approach to reduce nitrated synuclein enlightens the way of PD treatment. Recently, hytrin has emerged as a neurotherapeutic agent that activates IDH2 in synucleinopathy alleviation. However, burst release kinetics hamper the therapeutic efficacy of hytrin. We included our reported hytrin-loaded polydopamine-serotonin nanoparticles and utilized them for the investigation of therapeutic efficacy and molecular insights of neuroprotective action in an in vivo PD model with the aim to improve the therapeutic efficacy of hytrin. The present study explored behavioral testing, immunohistochemistry, and protein expression analysis to understand the camouflaged role of IDH2 in the activation of chaperone-mediated autophagy in the reduction of nitrated synuclein. The nanoformulation exhibited a neuroprotective efficiency through improved behavioral changes against PD deficits. The neuroprotective action has been attributed to IDH2-mediated Hsc70/Lamp2a induction in the reduction of nitrated synuclein. This study revealed the hytrin nanoformulation effect in the activation of chaperone-mediated autophagy to alleviate nitrated synucleinopathy in PD treatment.

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Section: Methodsmentioning

confidence: 99%

Hytrin Nanoformulation Reduces Nitrated Synucleinopathy Through Chaperon-Mediated Autophagy

Sardoiwala,

Boddu,

Biswal

et al. 2024

ACS Appl. Nano Mater.

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“…FTY720 was reported to be highly protective in this model. Another laboratory tested FTY720-Chitosan against a rotenone model and also saw protection [60].…”

Section: Rotenone Modelmentioning

confidence: 99%

Preclinical Validation of FTY720 and FTY720-Mitoxy in Mouse Models of Parkinsons Disease and Multiple System Atrophy (MSA): Evidence for Treating Lewy Body Disease Synucleinopathies Including MSA

Vidal-Martinez,

Lou,

G. Perez

2024

Rare Neurodegenerative Disorders - New Insights [Working Title]

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We assessed FTY720 and our patented-mitochondria-localizing-FTY720-derivative, FTY720-Mitoxy, in mouse models of Parkinson’s disease (PD) and MSA. FTY720 and FTY720-Mitoxy were given by gavage, injection, or osmotic pump. We used symptomatic transgenic alpha-Synuclein (aSyn) PD mice (A53T aSyn) and MSA mice (CNP-aSyn), as well as transgenic GM2 +/− PD mice. We also tested toxin PD and MSA models. We measured movement, constipation, gut motility, sweat ability, and bladder function. We counted blood lymphocytes 24 h after FTY720 or FTY720-Mitoxy. We measured Brain Derived Neurotrophic Factor (BDNF), Glial Cell Line Derived Neurotrophic Factor (GDNF), and Nerve Growth Factor (NGF) mRNA and protein. We assessed aSyn insolubility in gut, brain, and spinal cord by sequential protein extraction and immunoblot. We assessed fecal genomic DNA using 16S rRNA sequencing. In PD mice FTY720 normalized body and gut movement, urinary bladder function while increasing trophic factors and eliminating synucleinopathy. In MSA mice FTY720-Mitoxy normalized body and gut movement, sweat ability, mitochondrial function, improved microbiota while increasing trophic factors and eliminating synucleinopathy. FTY720 and FTY720-Mitoxy improve function and counteract synucleinopathy. As FTY720-Mitoxy is not immunosuppressive, it may be safer for treating PD and/or MSA.

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Antibody conjugated targeted nanotherapy epigenetically inhibits calpain-mediated mitochondrial dysfunction to attenuate Parkinson’s disease

Biswal,

Sahu,

Sardoiwala

et al. 2024

Carbohydrate Polymers

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FTY720 Nanoformulation Induces O-GlcNacylation of Synuclein to Alleviate Synucleinopathy

Cited by 3 publications

References 32 publications

Hytrin Nanoformulation Reduces Nitrated Synucleinopathy Through Chaperon-Mediated Autophagy

Hytrin Nanoformulation Reduces Nitrated Synucleinopathy Through Chaperon-Mediated Autophagy

Preclinical Validation of FTY720 and FTY720-Mitoxy in Mouse Models of Parkinsons Disease and Multiple System Atrophy (MSA): Evidence for Treating Lewy Body Disease Synucleinopathies Including MSA

Antibody conjugated targeted nanotherapy epigenetically inhibits calpain-mediated mitochondrial dysfunction to attenuate Parkinson’s disease

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