Construct, Face, and Predictive Validity of Parkinson's Disease Rodent Models.

Parkinson's disease (PD) is the second most common neurodegenerative disease globally. Current drugs only alleviate symptoms without halting disease progression, making rodent models essential for researching new therapies and understanding the disease better. However, selecting the right model is challenging due to the numerous models and protocols available.

Evaluating a Venom-Bioinspired Peptide, NOR-1202, as an Antiepileptic Treatment in Male Mice Models.

Epilepsy, a neurological disorder characterized by excessive neuronal activity and synchronized electrical discharges, ranks among the most prevalent global neurological conditions. Despite common use, antiepileptic drugs often result in adverse effects and lack effectiveness in controlling seizures in temporal lobe epilepsy (TLE) patients. Recent research explored the potential of occidentalin-1202, a peptide inspired by venom, in safeguarding Wistar rats from chemically induced seizures.

Antiepileptic profile of Parawixin-11, purified from Parawixia bistriata spider venom (Araneae, Araneidae), in Wistar rats.

The pharmacological treatment of epilepsy is often complex due to the lack of efficacy in many patients and profound side effects from current drugs, including sedation, motor impairment, and teratogenesis. In the quest for new antiepileptic drugs, animal venoms offer a valuable source of neuroactive molecules targeting ion channels and neurotransmitter receptors. This study investigates the antiepileptic potential of compounds isolated from the venom of the Parawixia bistriata spider.

Fecal microbiota transplantation ameliorates high-fat diet-induced memory impairment in mice.

Gut dysbiosis is linked to metabolic and neurodegenerative diseases and comprises a plausible link between high-fat diet (HFD) and brain dysfunction. Here we show that gut microbiota modulation by either antibiotic treatment for 5 weeks or a brief 3-day fecal microbiota transplantation (FMT) regimen from low-fat (control) diet-fed mice decreased weight gain, adipose tissue hypertrophy, and glucose intolerance induced by HFD in C57BL/6 male mice. Notably, gut microbiota modulation by FMT completely reversed impaired recognition memory induced by HFD, whereas modulation by antibiotics had less pronounced effect.

New fraternine analogues: Evaluation of the antiparkinsonian effect in the model of Parkinson's disease.

Venom-derived peptides are important sources for the development of new therapeutic molecules, especially due to their broad pharmacological activity. Previously, our research group identified a novel natural peptide, named fraternine, with promising effects for the treatment of Parkinson's disease. In the present paper, we synthesized three peptides bioinspired in fraternine: fra-10, fra-14, and fra-24.

Innovative Pre-Clinical Data Using Peptides to Intervene in the Evolution of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model.

Early-life metabolic dysfunction impairs cognition and mitochondrial function in mice.

The impact of overnutrition early in life is not restricted to the onset of cardiovascular and metabolic diseases, but also affects critical brain functions related to cognition. This study aimed to evaluate the relationship between peripheral metabolic and bioenergetic changes induced by a two-hit protocol and their impact on cognitive function in juvenile mice. Three-week-old male C57BL/6 mice received a high-fat diet (HFD) or control diet for 7 weeks, associated with two low doses of streptozotocin (STZ) or vehicle.

A new class of peptides from wasp venom: a pathway to antiepileptic/neuroprotective drugs.

The ability of venom-derived peptides to disrupt physiological processes in mammals provides an exciting source for pharmacological development. Our research group has identified a new class of neuroactive peptides from the venom of a Brazilian social wasp, , with the potential pharmacological profile to treat epilepsies. The study was divided into five phases: Phase 1 concerned the extraction, isolation and purification of Occidentalin-1202(n) from the crude venom, followed by the synthesis of an identical analogue peptide, named Occidentalin-1202(s).

Challenges in the pharmacological treatment of patients under suspicion of chronic traumatic encephalopathy: A review.

Chronic traumatic encephalopathy (CTE) is caused by progressive neurodegeneration associated with repetitive head impacts. This disease is more common in professionals who practice contact sports, resulting in a concussion and subconcussive trauma. CTE is characterized by the accumulation of hyperphosphorylated tau protein in neurons, astrocytes, and frontotemporal lobe degeneration.

Parkinson's disease rodent models: Are they suitable for DBS research?

Deep brain stimulation (DBS) appeared in the therapeutic framework for Parkinson's disease in the late 1980 s and early 1990 s, conceived as an alternative to ablative treatments, using inhibitory electrical stimulation parameters still clinically in force today, with frequencies above 130 Hz, a pulse width of 60 ms and current intensity around 3 mA into deep brain structures, to relieve the motor symptoms of the disease. This context expands into a technique not only restricted to the targets traditionally used in lesional procedures, supported by the knowledge acquired with non-human primate (NHP) animal models during the early 1990 s, initiated by Benazzouz and collaborators. Currently, NHP animal models have lost ground to research models in rodents, which have assumed a prominent position in scientific research on DBS.

Innovative treatments for epilepsy: Venom peptides, cannabinoids, and neurostimulation.

Antiepileptic drugs have been successfully treating epilepsy and providing individuals sustained seizure freedom. However, about 30% of the patients with epilepsy present drug resistance, which means they are not responsive to the pharmacological treatment. Considering this, it becomes extremely relevant to pursue alternative therapeutic approaches, in order to provide appropriate treatment for those patients and also improve their quality of life.

Synthesis and biological evaluation of 4-hydroxy-methylpiperidinyl-N-benzyl-acylarylhydrazone hybrids designed as novel multifunctional drug candidates for Alzheimer's disease.

The search for new drug candidates against Alzheimer's disease (AD) remains a complex challenge for medicinal chemists due to its multifactorial pathogenesis and incompletely understood physiopathology. In this context, we have explored the molecular hybridization of pharmacophore structural fragments from known bioactive molecules, aiming to obtain a novel molecular architecture in new chemical entities capable of concomitantly interacting with multiple targets in a so-called multi-target directed ligands (MTDLs) approach. This work describes the synthesis of 4-hydroxymethyl)piperidine-N-benzyl-acyl-hydrazone derivatives 5a-l, designed as novel MTDLs, showing improved multifunctional properties compared to the previously reported parent series of N-benzyl-(3-hydroxy)piperidine-acyl-hydrazone derivatives 4.

Design, synthesis, and biological evaluation of new thalidomide-donepezil hybrids as neuroprotective agents targeting cholinesterases and neuroinflammation.

A new series of eight multifunctional thalidomide-donepezil hybrids were synthesized based on the multi-target-directed ligand strategy and evaluated as potential neuroprotective, cholinesterase inhibitors and anti-neuroinflammatory agents against neurodegenerative diseases. A molecular hybridization approach was used for structural design by combining the -benzylpiperidine pharmacophore of donepezil and the isoindoline-1,3-dione fragment from the thalidomide structure. The most promising compound, PQM-189 (3g), showed good AChE inhibitory activity with an IC value of 3.

Octovespin, a peptide bioinspired by wasp venom, prevents cognitive deficits induced by amyloid-β in Alzheimer's disease mouse model.

Approximately 46.8 million people have been diagnosed worldwide with dementia, of which the most common type is Alzheimer's disease (AD). Since the current AD treatment is incipient and limited, it is essential to develop new drugs to prevent AD.

Therapeutic nanoparticles in the brain: A review of types, physicochemical properties and challenges.

One of the main obstacles in the treatment of neurological diseases, perhaps the biggest one, is the delivery of therapeutic compounds to the central nervous system, and nanoparticles are promising tools to overcome this challenge. Different types of nanoparticles may be used as delivery systems, including liposomes, carbon nanotubes, and dendrimers. Nevertheless, these nanoparticles must display characteristics to be useful in brain drug delivery, such as stability, permeability to blood vessels, biocompatibility, and specificity.

Current knowledge, challenges, new perspectives of the study, and treatments of Autism Spectrum Disorder.

Over the past 70 years, the understanding of Autism Spectrum Disorder (ASD) improved greatly and is characterized as a heterogeneous neuropsychiatric syndrome. ASD is characterized by difficulties in social communication, restricted and repetitive behavior, interests, or activities. And it is often described as a combination of genetic predisposition and environmental factors.

Dopamine-loaded nanoparticle systems circumvent the blood-brain barrier restoring motor function in mouse model for Parkinson's Disease.

Parkinson's disease (PD) is a progressive and chronic neurodegenerative disease of the central nervous system. Early treatment for PD is efficient; however, long-term systemic medication commonly leads to deleterious side-effects. Strategies that enable more selective drug delivery to the brain using smaller dosages, while crossing the complex brain-blood barrier (BBB), are highly desirable to ensure treatment efficacy and decrease/avoid unwanted outcomes.

Macrophage activation in vitro by Parachartergus fraternus venom.

Parachartergus fraternus wasp induces inflammation with a predominance of mononuclear cells, that can acquire macrophage functions at the sting site, amplifying the response. These cells can be activated by venomous animals and are involved in destruction of injurious agents and release of inflammatory mediators. The objective of this work was to evaluate the activity of P.

Antiseizure potential of peptides from the venom of social wasp Chartergellus communis against chemically-induced seizures.

Epilepsy is one of the most common neurological diseases in the world. The objective of this research was to investigate a new peptide from the venom of the social wasp Chartergellus communis useful to the study or pharmacotherapy of epilepsy. The wasps were collected, and their venom was extracted.

Ischemia-induced retinal injury is attenuated by Neurovespina, a peptide from the venom of the social wasp Polybia occidentalis.

Neurovespina is a synthetic peptide modified from Occidentalin-1202, a nine amino acid residue peptide isolated from the venom of the social wasp Polybia occidentalis. Previous studies showed that this peptide has a neuroprotective effect on the central nervous system, but its action on the eye has not been explored. So, the objective of this work was to investigate the neuroprotective effect of Neurovespina on the retina and its angiogenic potential in the chicken chorioallantoic membrane (CAM).

Pro-inflammatory response induced by the venom of Parachartergus fraternus wasp.

The sting of different wasp species triggers local and systemic reactions in victims that can lead to death. Parachartergus fraternus is responsible for frequent accidents in Latin America; however, few studies have been conducted on this insect and its venom. In this study, the inflammatory process induced by the venom of the P.

Fraternine, a Novel Wasp Peptide, Protects against Motor Impairments in 6-OHDA Model of Parkinsonism.

Parkinson's disease (PD) is a progressive neurodegenerative condition that affects the Central Nervous System (CNS). Insect venoms show high molecular variability and selectivity in the CNS of mammals and present potential for the development of new drugs for the treatment of PD. In this study, we isolated and identified a component of the venom of the social wasp and evaluated its neuroprotective activity in the murine model of PD.

Neuropolybin: A new antiseizure peptide obtained from wasp venom.

Epilepsy accounts for one of the most serious neurological disorders, and its treatment remains a challenge, due to high cost and harmful side effects. Bioactive molecules extracted from arthropod venoms are considered a promising therapy since these compounds are known for their highly selective and potent profiles. The purpose of this study was to identify and characterize the potential antiseizure effect of the peptide Ppnp7, extracted from the venom of the social wasp Polybia paulista, and also the effect of the bioinspired peptide, named Neuropolybin, in the same parameters.