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- | Journal: Deep convolutional neural network-based identification and biological evaluation of MAO-B inhibitors. (Pubmed Central) - Nov 19, 2024
Additionally, the study also underscored the utility of scaffold analysis as an effective way for evaluating the significance of structurally diverse compounds in data-driven investigations. We believe that our models are able to pick up diverse chemotype and this can be a starting scaffold for further structural optimization with medicinal chemistry efforts in order to improve their inhibition efficacy and be established as novel MAO-B inhibitors in the furture.
- | Retrospective data, Journal: Anti-obesity effect of irreversible MAO-B inhibitors in patients with Parkinson's disease. (Pubmed Central) - Nov 19, 2024
The results suggested that short-term administration of iMAO-Bi may have potential weight-loss effects. Further studies with larger sample sizes are needed to evaluate the weight-loss effect of iMAO-Bi.
- | Xadago (safinamide) / Meiji Seika, Zambon, Supernus Pharma, mexiletine / Generic mfg.
Preclinical, Journal: Preclinical study of the antimyotonic efficacy of safinamide in the myotonic mouse model. (Pubmed Central) - Nov 16, 2024
Safinamide was able to reduce the TRR in ADR mice to a greater extent than mexiletine. In conclusion, safinamide counteracted the abnormal muscle hyperexcitability in myotonic mice both in vitro and in vivo suggesting it as an effective drug to be indicated in Myotonia Congenita.
- | haloperidol / Generic mfg.
Biomarker, Preclinical, Journal: Effects of Acute Haloperidol Treatment on Dopaminergic Markers, GAD67, and A2A Receptors in Rats with High and Low VCMs. (Pubmed Central) - Nov 16, 2024
Further studies could clarify the main targets involved in the motor side effects of antipsychotics. The present study demonstrated an easy way to separate the animals into High and Low VCMs.
- | Preclinical, Journal, Tau PET: Synthesis and preclinical evaluation of diarylamine derivative as Tau-PET radiotracer for Alzheimer's Disease. (Pubmed Central) - Nov 16, 2024
Satisfactorily, [18F]FA1 fulfilled critical requirements as a Tau radiotracer, demonstrating high specificity and selectivity for Tau, a clean off-target profile against A? plaques and monoamine oxidase B (MAO-B), and favorable in vivo brain kinetics, as confirmed by dynamic PET studies in rodents and non-human primates.
- | aripiprazole / Generic mfg.
Journal: Exploring the potential pharmacological mechanism of aripiprazole against hyperprolactinemia based on network pharmacology and molecular docking. (Pubmed Central) - Nov 15, 2024
Molecular docking results demonstrate a favorable affinity between aripiprazole and the core target proteins MAO-B, DRD2, SLC6A3, HTR2C, HTR2A, CYP2D6, DRD4, and DRD1. Network pharmacology predicted potential targets and signaling pathways for aripiprazole's intervention in hyperprolactinemia, offering theoretical support and a reference basis for optimizing clinical strategies and drug development involving aripiprazole.
- | Journal: Evidence of altered monoamine oxidase B, an astroglia marker, in early psychosis and high-risk state. (Pubmed Central) - Nov 15, 2024
Lower MAO-B concentration supports astrocyte dysfunction in cannabis-using CHR and FEP clinical populations. Lower MAO-B is consistent with replicated striatal dopamine elevation in psychosis, as well as astrocyte dysfunction in schizophrenia.
- | Journal: Network Pharmacology and Experimental Validation Reveal the Mechanisms of Sniffing Essential Oil of Acori Tatarinowii Rhizoma in Treating Olfactory Dysfunction. (Pubmed Central) - Nov 14, 2024
EOAT inhalation could improve olfactory function in 3-MI-induced OD model. The underlying mechanism may be related to the modulation of the PI3K/Akt signaling pathway.
- || Parkinsan (budipine) / Lundbeck, Takeda
Clinical guideline, Review, Journal: Pharmacotherapy of motor symptoms in early and mid-stage Parkinson's disease: guideline "Parkinson's disease" of the German Society of Neurology. (Pubmed Central) - Nov 13, 2024
The recommendations for the pharmacotherapy of motor symptoms of PD have been updated. Newly available drugs have been added, while other drugs (e.g., ergoline dopamine agonists, anticholinergics, budipine) have been removed from the recommendations.
- | Journal: Exploring natural products as multi-target-directed drugs for Parkinson's disease: an in-silico approach integrating QSAR, pharmacophore modeling, and molecular dynamics simulations. (Pubmed Central) - Nov 13, 2024
These results may serve as lead compounds for the development and optimization of natural products as multi-target disease-modifying natural remedies for Parkinson's disease patients. However, experimental assays remain necessary to validate these findings.Communicated by Ramaswamy H. Sarma.
- Characteristics of the threshold tracking TMS and 18FTHK5351 PET for the detection of ALS lesions in the primary motor cortex (Poster Hall at the Palais de Congres Montreal; 517b/c) - Nov 7, 2024 - Abstract #ALSMND2024ALS_MND_548;
T-TMS and 18F-THK5351 PET were similarly sensitive for detecting lesions in the PMC, except in patients with UL onset disease. T-TMS can detect cortical hyperexcit-ability prior to IE associated with astrogliosis in the PMC, as we previously reported, leading to a higher diagnostic sensitivity of T-TMS in patients with UL onset.
- | Journal: Parkinson's Disease: Unravelling the Medicinal Perspectives and Recent Developments of Heterocyclic Monoamine Oxidase-B Inhibitors. (Pubmed Central) - Nov 6, 2024
The review covers in vitro, in silico, and in vivo data, along with the structure- activity relationship of these compounds. These findings offer valuable insights for the development of more effective MAO-B inhibitors and advancements in Parkinson's disease research.
- | Journal: Novel coumarin benzamides as potent and reversible monoamine oxidase-B inhibitors: Design, synthesis, and neuroprotective effects. (Pubmed Central) - Nov 4, 2024
Moreover, molecular docking and molecular dynamics simulations highlighted the tight interactions of 3i with Tyr398 at the binding site of MAO-B. These findings suggest that 3i is a potent, reversible, and selective MAO-B inhibitor that could potentially treat neurological disorders.
- | Xadago (safinamide) / Meiji Seika, Zambon, Supernus Pharma
Preclinical, Journal: Functional efficacy of the MAO-B inhibitor safinamide in murine substantia nigra pars compacta dopaminergic neurons in vitro: A comparative study with tranylcypromine. (Pubmed Central) - Nov 3, 2024
According to our results, SAF marginally potentiates the DA signal in SNpc DAergic neurons, while exerting an inhibitory effect on the postsynaptic excitability acting on membrane conductances. Thus, we propose that the therapeutic effects of SAF in PD patients partially depends on MAO inhibition, while other MAO-independent sites of action could be more relevant.
- | Journal: Living with Parkinson's disease in Portugal: Findings from PRISM study. (Pubmed Central) - Nov 3, 2024
This study uncovers the burden of PD among Portuguese patients, revealing current treatment methods, impact on daily life and healthcare resources employed in Portugal. It emphasizes the need for personalized clinical strategies at national and international levels to improve long-term health outcomes and quality of life of PD patients.
- | Journal: 18F-THK5351 PET Is Superior to Conventional MRI in Identifying Inflammatory Lesions by Imaging Astrogliosis in 2 Cases of Neurosyphilis. (Pubmed Central) - Nov 1, 2024
Here, we present 2 cases of neurosyphilis, in which 18F-THK5351 PET identified inflammatory lesions by imaging astrogliosis, whereas MRI had difficulty detecting the lesions. Hence, this study suggests that 18F-THK5351 PET is superior to conventional MRI in identifying inflammatory lesions and that this feature of 18F-THK5351 can provide insights into the pathophysiology of neurosyphilis in living patients.
- | Journal: Reactive Astrocytes Promote Axonal Remodeling of the Corticospinal Tract During Neuronal Recovery Revealed by 18F-THK5351 PET. (Pubmed Central) - Nov 1, 2024
Recently, the beneficial role of RAs in plasticity and reconstruction after traumatic brain injury has been reported. 18F-THK5351 uptake may represent axonal remodeling accompanied with RAs in the CST.
- | Journal: Parkinson's Disease: A Progressive Neurodegenerative Disorder and Structure-Activity Relationship of MAO Inhibitor Scaffolds as an Important Therapeutic Regimen. (Pubmed Central) - Nov 1, 2024
The treatment of Parkinson's disease with MAO inhibitors has shown promising outcomes. Herein, we reported characteristic features of Parkinson's disease, various treatment strategies, and the SAR of potential drugs that can be explored further as lead for the development of newer molecules with improved pharmacological profiles.
- | Preclinical, Journal: Multiomics analysis reveals the potential mechanism of high-fat diet in dextran sulfate sodium-induced colitis mice model. (Pubmed Central) - Oct 31, 2024
Overall, the findings indicate that the impact of HFD on DSS-induced colitis may be linked to intestinal dysbiosis and specific genes such as Abca8b, Ace2, Apoa1, Apoa4, Apoc3, Aspa, Dpp4, Maob, Slc34a2, Slc7a9, and Trpm6. These results provide valuable insights for determining potential therapeutic targets for addressing HFD-induced IBD.
- | Journal: Potential MAO-B Inhibitors from Cissampelos capensis L.f.: ADMET, Molecular Docking, Dynamics, and DFT Insights. (Pubmed Central) - Oct 29, 2024
MD simulations supported these findings, showing stable interactions with MAO-B, while Density Functional Theory (DFT) calculations highlighted the electrophilic nature of cissamanine, enhancing its potential as an effective inhibitor. These results advocate further in vitro and in vivo studies to evaluate their potential as PD therapeutics.
- | Preclinical, Journal: Intermittent access to sugary drinks associated with fasting induces overeating and depressive-like behavior in female C57BL/6J mice. (Pubmed Central) - Oct 27, 2024
In a separate design (Experiment 2), groups with 16 and 20?h of fasting alone (without sucrose) did not show the same behavioral results as the intermittent fasting sucrose groups, thus avoiding fasting bias. Based on these results, the 20-hour sucrose fasting group was chosen as the ideal protocol for mimicking overeating behavior associated with depression to investigate future therapeutic approaches for this comorbidity.
- | rivastigmine / Generic mfg.
Journal: Rivastigmine structure-based hybrids as potential multi-target anti-Alzheimer's drug candidates. (Pubmed Central) - Oct 26, 2024
All these promising rivastigmine-like hybrids were assayed for their pharmacokinetic properties by using different bio-analytical techniques, showing interesting applicability profiles. Moreover, cytotoxicity assays displayed a safety profile on three different cell lines.
- || selegiline / Generic mfg., rasagiline / Generic mfg.
PK/PD data, Journal: Design, Synthesis, Molecular Docking, Pharmacokinetic Properties, and Molecular Dynamics Simulation of Sulfonyl Derivatives of Benzimidazole against Parkinson's Disease. (Pubmed Central) - Oct 25, 2024
Moreover, cytotoxicity assays displayed a safety profile on three different cell lines. This study indicates that the binding affinity of most of the hits was superior to that of known MAO inhibitors; therefore, these newly synthesized benzimidazole derivatives may be developed into essential drug candidates for the treatment of PD.
- | Journal: Target Fisher: a Consensus Structure-Based Target Prediction Tool, and its Application in the Discovery of Selective MAO-B Inhibitors. (Pubmed Central) - Oct 24, 2024
In this sense, Target Fisher is a valuable tool to aid organic and medicinal chemistry groups in target identification, drug discovery and drug repurposing. As a case study, we demonstrate the efficacy of Target Fisher by screening a small library of assorted natural products for targets relevant to neurodegenerative diseases, which resulted in the identification and experimental validation of selective inhibitors of monoamine oxidase B (MAO-B).
- | Rexulti (brexpiprazole) / Lundbeck, Otsuka
Journal: Identification of high-affinity Monoamine oxidase B inhibitors for depression and Parkinson's disease treatment: bioinformatic approach of drug repurposing. (Pubmed Central) - Oct 24, 2024
Simulation results demonstrated that the binding of Brexpiprazole and Trifluperidol induced only minor structural alterations in MAO-B and showed significant stabilization throughout the simulation trajectory. Overall, the finding suggests that Brexpiprazole and Trifluperidol exhibit strong potential as repurposed inhibitors of MAO-B that might be explored further in experimental investigations for the development of targeted therapies for depression and PD.
- | pramipexole IR / Generic mfg.
Preclinical, Journal: Chronic pramipexole and rasagiline treatment enhances dendritic spine structural neuroplasticity in striatal and prefrontal cortex neurons of rats with bilateral intrastriatal 6-hydroxydopamine lesions. (Pubmed Central) - Oct 23, 2024
In nucleus accumbens (NAcc) SPNs and prefrontal cortex layer 3 (PFC-3) pyramidal cells, dendritic spine density remained unaltered, but PPX-Ras decreased mushroom spines and increased bifurcated spines in the NAcc, while increasing mushroom spines and decreasing stubby spines in PFC-3 in lesioned rats. These findings emphasize the importance of dendritic spines as promising targets for innovative pharmacotherapies for Parkinson's disease.
- | Xadago (safinamide) / Meiji Seika, Zambon, Supernus Pharma, Nourianz (istradefylline) / Kyowa Kirin
Journal: Computational exploration of acefylline derivatives as MAO-B inhibitors for Parkinson's disease: insights from molecular docking, DFT, ADMET, and molecular dynamics approaches. (Pubmed Central) - Oct 23, 2024
These results were also validated by simulation-based binding free energies via the molecular mechanics energies combined with generalized Born and surface area solvation (MM-GBSA) method. However, it is necessary to conduct in vitro and in vivo experiments to confirm and validate these findings in future studies.
- | Xadago (safinamide) / Meiji Seika, Zambon, Supernus Pharma
Preclinical, Journal: Inhibition of monoamine oxidases by heterocyclic derived conjugated dienones: synthesis and in vitro and in silico investigations. (Pubmed Central) - Oct 21, 2024
Both lead compounds exhibited similar potencies to safinamide and were more potent than pargyline...The study results indicated that all the compounds evaluated demonstrated potent inhibition of MAO-B activity, which was comparable to the efficacy of reference medications. It is necessary to do further investigations on the lead molecules to see whether they may be used to treat different neurodegenerative illnesses.
- | Journal: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated adult zebrafish as a model for Parkinson's Disease. (Pubmed Central) - Oct 19, 2024
Despite its benefits, this model does not appear to recapitulate full pathophysiology of the disease with the full profile of expected gene downregulation. Because of this, it is important that researchers looking for pharmacological interventions for PD only use this zebrafish model when targeting the human-relevant PD symptoms and causes that are represented.
- | Journal: Design, synthesis and biological evaluation of novel benzocoumarin derivatives as potent inhibitors of MAO-B activity. (Pubmed Central) - Oct 19, 2024
Inhibition mode of A6 on MAO-B was predicted as mixed reversible inhibition with a Ki value of 3.274?nM. Furthermore, in order to elaborate structure-activity relationships, the binding mode of A6 was investigated by molecular docking simulations.
- A Novel Mao-A Gene variant: Brunner syndrome, a Rare syndrome, is Associated with a Wide Range of Psychiatric Symptoms. (Summit 1, 3rd Floor) - Oct 19, 2024 - Abstract #WCPG2024WCPG_265;
He was brought to our clinic with complaints of 'attention problems and biting objects'. It was learned that his maximum focusing time was 1-2 minutes and he had difficulty in doing homework, constantly fell and was clumsy, spilled food, often lost his belongings and tore objects such as pencils, erasers, pillow edges with his teeth, had difficulty in tying laces and buttoning.
- | Journal: Exploring the 1-(4-Nitrophenyl)-3-arylprop-2-en-1-one Scaffold for the Selective Inhibition of Monoamine Oxidase B. (Pubmed Central) - Oct 16, 2024
Conversely, their activity toward the A isozyme was only observed at micromolar concentrations. Our results bear out the hypothesis that the 1,3-diarylpropenone scaffold could represent a valuable starting point for designing efficient and selective MAO-B inhibitors.
- || Review, Journal: Perry Disease: Current Outlook and Advances in Drug Discovery Approach to Symptomatic Treatment. (Pubmed Central) - Oct 16, 2024
For each of the chosen targets, based on the resolved protein-ligand structures deposited in the Protein Data Bank (PDB) database, pharmacophore models are proposed. We review novel, active compounds that might serve as either hits for further optimization or candidates for further phases of studies, leading to potential use in the treatment of PeD.
- | Biomarker, Journal, Tumor microenvironment, Tumor-infiltrating lymphocyte, IO biomarker: Modulation of the tumor microenvironment in non-muscle-invasive bladder cancer by OncoTherad (Pubmed Central) - Oct 15, 2024
The IS revealed improvements in immune responses post-treatment, with higher scores associated with better RFS and PCR outcomes. These findings validate OncoTherad
- | Journal: Mannich reaction mediated derivatization of chromones and their biological evaluations as putative multipotent ligands for the treatment of Alzheimer's disease. (Pubmed Central) - Oct 14, 2024
In enzyme kinetic inhibition studies, these compounds showed mixed-type inhibition to AChE. In the computational studies, binding interactions, and orientations of the ligands at the active site of the enzymes were analyzed and these lead compounds were found to be thermodynamically stable inside the active cavity for up to 100 ns.
- || Review, Journal: A comprehensive review of natural compounds and their structure-activity relationship in Parkinson's disease: exploring potential mechanisms. (Pubmed Central) - Oct 11, 2024
This review will also explore the structure-activity relationship (SAR) of these compounds and assess the clinical studies investigating the impact of these natural compounds on individuals with PD. The insights shared in this review have the potential to pave the way for the development of innovative therapeutic strategies and interventions for PD.
- | Preclinical, Journal: Design, synthesis, in vitro, and in silico study of benzothiazole-based compounds as a potent anti-Alzheimer agent. (Pubmed Central) - Oct 7, 2024
It also revealed several important interactions, particularly hydrogen bonding interaction. All the newly synthesized compounds showed good ADME pharmacokinetic profile and followed Lipinski rule; these compounds represent promising hits for the development of promising lead compounds for AD treatment.
- Targeting Monoamine Oxidase B in Dystrophic mdx Hearts Dampens Inflammation and Fibrosis (Zone 1' Science & Technology Hall) - Oct 7, 2024 - Abstract #AHA2024AHA_9079;
- | Xadago (safinamide) / Meiji Seika, Zambon, Supernus Pharma
Journal: Safinamide effect on sleep architecture of motor fluctuating Parkinson's disease patients: A polysomnographic rasagiline-controlled study. (Pubmed Central) - Oct 3, 2024
All the newly synthesized compounds showed good ADME pharmacokinetic profile and followed Lipinski rule; these compounds represent promising hits for the development of promising lead compounds for AD treatment. This study showed that safinamide, in addition to having a significant effect on PD motor symptoms, like the other MAOB-Is, may exert a specific beneficial effect on subjective and objective sleep, probably driven by its dual mechanism of action, which involves both dopaminergic and glutamatergic neurotransmission.
- | selegiline / Generic mfg.
Preclinical, Journal: Neurotoxicity, Neuroprotection, In Vitro MAOA/MAOB Inhibitory Activity Assessment, Molecular Docking, and Permeability Assay Studies of Newly Synthesized Hydrazones Containing a Pyrrole Ring. (Pubmed Central) - Sep 29, 2024
stabilization with the aromatic pyrrole ring. The preliminary PAMPA testing indicated that in relation to the blood-brain barrier (BBB) permeability, the tested pyrrole-based hydrazones may be considered as high permeable, except for 8a and 8e, which were established to be permeable in the medium range with -logP of 5.268 and 5.714, respectively, compared to the applied references.
- | Journal: Comparative Analysis of Volatile Components in Chi-Nan and Ordinary Agarwood Aromatherapies: Implications for Sleep Improvement. (Pubmed Central) - Sep 29, 2024
The results suggest that agarwood aromatherapy enhances sleep quality through both hormonal and neurotransmitter pathways, with ordinary agarwood more deeply mediating hormonal regulation, while Chi-Nan agarwood predominantly influences neurotransmitter pathways, particularly those involving serotonin and GABA. This study provides valuable insights into the distinct therapeutic potentials of Chi-Nan and ordinary agarwood, highlighting their roles in sleep improvement and offering a foundation for future research in the clinical application of agarwood-based aromatherapy.
- | Journal: Novel Pyrrole Derivatives as Multi-Target Agents for the Treatment of Alzheimer's Disease: Microwave-Assisted Synthesis, In Silico Studies and Biological Evaluation. (Pubmed Central) - Sep 29, 2024
The ADME and in vitro PAMPA studies demonstrated that vh0 could cross the blood-brain barrier, and it poses good lead-like properties. Moreover, the optimized molecular structures and the frontier molecular orbitals were examined via DFT studies at 6-311G basis set in the ground state.
- | Journal: Unraveling the Liver-Brain Axis: Resveratrol's Modulation of Key Enzymes in Stress-Related Anxiety. (Pubmed Central) - Sep 29, 2024
We demonstrate that resveratrol exerts antianxiogenic effects by modulating glucocorticoid and monoamine metabolism in the brain and liver. These findings suggest resveratrol's potential as a therapeutic agent for anxiety disorders, warranting further clinical investigation.
- Investigation of vermal [18F]PI-2620 signal and its sex-related differences in dynamic tau-PET imaging (e-Poster Area) - Sep 27, 2024 - Abstract #EANM2024EANM_2022;
Our results suggest that vermal tau accumulation and leptomeningeal pigmented cells contribute to vermal [18F]PI-2620 uptake. Further investigation will include sex-specific signal sources as well as kinetic parameters and microautoradiography to decipher the signal origin at cellular level.
- Effective production of (S)-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline ([18F]SMBT-1) on an iPHASE Flexlab radiochemistry module for in vivo imaging of a rat model with traumatic brain injury (e-Poster Area) - Sep 27, 2024 - Abstract #EANM2024EANM_1465;
Synthesis of the SMBT-1 precursor for radiolabelling was achieved in good yields, then successfully radiolabelled with 18fluoride in high radiochemical yield to afford the radiotracer [18F]SMBT-1. Imaging of a rat model following unilateral fluid percussion injury showed increased uptake in the affected hippocampus.
- | Preclinical, Journal: Investigating In Silico and In Vitro Therapeutic Potential of Diosmetin as the Anti-Parkinson Agent. (Pubmed Central) - Sep 26, 2024
Imaging of a rat model following unilateral fluid percussion injury showed increased uptake in the affected hippocampus. Diosmetin possibly acts on several target receptors linked to the pathophysiology of PD, demonstrating promise as an OS inhibitor and scavenger.
- | Journal: Shaoyao Gancao Decoction Mitigates Helicobacter Pylori-Induced Chronic Atrophic Gastritis by Suppressing MAOB. (Pubmed Central) - Sep 25, 2024
Diosmetin possibly acts on several target receptors linked to the pathophysiology of PD, demonstrating promise as an OS inhibitor and scavenger. No abstract available
- | donepezil / Generic mfg., betahistine / Generic mfg., rasagiline / Generic mfg.
Preclinical, Journal: Pharmacological intervention of behavioural traits and brain histopathology of prenatal valproic acid-induced mouse model of autism. (Pubmed Central) - Sep 24, 2024
Therefore, the aim of this study was to evaluate the neuro-behavioural effects of Betahistine, an H3R antagonist, and Donepezil, an acetylcholinesterase inhibitor on Swiss albino mouse model of autism...The behavioural Y-Maze test exhibits significant improvement (p <0.01) on the short term memory of the test subjects upon administration of lower dose of Betahistine along with MAO-B inhibitor Rasagiline once compared with the NC1 group (VPA-exposed mice)...The effects found are dose dependent. The findings suggest that H3R might be a viable target for the treatment of ASD.
- | Journal: Predictive Analysis of Yi-Gai-San's Multifaceted Mechanisms for Tremor-Dominant Parkinson's Disease via Network Pharmacology and Molecular Docking Validation. (Pubmed Central) - Sep 24, 2024
The findings suggest that H3R might be a viable target for the treatment of ASD. From these computational findings, we suggested that YGS might mitigate PD-DT via "multi-compounds, multi-targets, and multi-pathways.".
- | Journal: Recent Developments in Coumarin Derivatives as Neuroprotective Agents. (Pubmed Central) - Sep 24, 2024
From these computational findings, we suggested that YGS might mitigate PD-DT via "multi-compounds, multi-targets, and multi-pathways.". Various studies have demonstrated the neuroprotective activity of coumarin due to an oxaheterocyclic loop, which allows binding with a broad array of proteins, thus motivating researchers to explore its potential as a lead against various neurodegenerative diseases.