Understanding the physiopathology of Alzheimer’s disease (AD) has improved substantially based on... more Understanding the physiopathology of Alzheimer’s disease (AD) has improved substantially based on studies of mouse models mimicking at least one aspect of the disease. Many transgenic lines have been established, leading to amyloidosis but lacking neurodegeneration. The aim of the current study was to generate a novel mouse model that develops neuritic plaques containing the aggressive pyroglutamate modified amyloid-β (pEAβ) species in the brain. The TAPS line was developed by intercrossing of the pEAβ-producing TBA2.1 mice with the plaque-developing line APPswe/PS1ΔE9. The phenotype of the new mouse line was characterized using immunostaining, and different cognitive and general behavioral tests. In comparison to the parental lines, TAPS animals developed an earlier onset of pathology and increased plaque load, including striatal pEAβ-positive neuritic plaques, and enhanced neuroinflammation. In addition to abnormalities in general behavior, locomotion, and exploratory behavior, TA...
Approximately 46.8 million people have been diagnosed worldwide with dementia, of which the most ... more 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. Considering that evolutionary pressure selected animal venom compounds that are very specific for a unique target, those can be a potential drug against AD. Octovespin was modified from occidentalin-1202, which is a peptide isolated from Polybia occidentalis wasp venom. In this context, this study evaluated the effect of treatment with octovespin against Amyloid-β (Aβ)-induced toxicity, which is postulated to be one of the main causes of AD, in both in vitro and in vivo tests. In vitro, octovespin was able to prevent Aβ aggregation in a ThT assay. In vivo, octovespin (0.15 nmol/animal) reverses memory impairment that is due to Aβ toxicity, in the Morris Water Maze and Novel Object Recognition Test. Our results suggested that octovespin is a potential drug for the treatment of AD, due to its ability to avoid Aβ aggregation in vitro and to prevent Aβ -induced memory deficit in mice.
The contribution of mouse models for basic and translational research at different levels is impo... more The contribution of mouse models for basic and translational research at different levels is important to understand neurodegenerative diseases, including tauopathies, by studying the alterations in the corresponding mouse models in detail. Moreover, several studies demonstrated that pathological as well as behavioral changes are influenced by the sex. For this purpose, we performed an in-depth characterization of the behavioral alterations in the transgenic Tau-P301L mouse model. Sex-matched wild type and homozygous Tau-P301L mice were tested in a battery of behavioral tests at different ages. Tau-P301L male mice showed olfactory and motor deficits as well as increased Tau pathology, which was not observed in Tau-P301L female mice. Both Tau-P301L male and female mice had phenotypic alterations in the SHIRPA test battery and cognitive deficits in the novel object recognition test. This study demonstrated that Tau-P301L mice have phenotypic alterations, which are in line with the his...
Multiple sources of evidence suggest that soluble amyloid β (Aβ)-oligomers are responsible for th... more Multiple sources of evidence suggest that soluble amyloid β (Aβ)-oligomers are responsible for the development and progression of Alzheimer’s disease (AD). In order to specifically eliminate these toxic Aβ-oligomers, our group has developed a variety of all-d-peptides over the past years. One of them, RD2, has been intensively studied and showed such convincing in vitro and in vivo properties that it is currently in clinical trials. In order to further optimize the compounds and to elucidate the characteristics of therapeutic d-peptides, several rational drug design approaches have been performed. Two of these d-peptides are the linear tandem (head-to-tail) d-peptide RD2D3 and its cyclized form cRD2D3. Tandemization and cyclization should result in an increased in vitro potency and increase pharmacokinetic properties, especially crossing the blood–brain-barrier. In comparison, cRD2D3 showed a superior pharmacokinetic profile to RD2D3. This fact suggests that higher efficacy can be a...
Besides a large variety of research on Alzheimer’s disease (AD), there are still open questions r... more Besides a large variety of research on Alzheimer’s disease (AD), there are still open questions regarding its pathophysiology. In this context, the development of a new transgenic mouse model TAPS, a genetic combination of heterozygous APP‐PS1dE9 and TBA2.1 mice, was accomplished. The TBA2.1 line expresses truncated amyloid‐β (Q3‐42), which is post‐translationally modified to pyroglutamate amyloid‐β (pE‐Aβ). Since this species of Aβ has been shown to be particularly cytotoxic and induces neurodegeneration in transgenic mice, TAPS mice were developed to mimic the combined human pathology of AD with amyloidosis and neurodegeneration.
Parkinson's disease (PD) is a neurodegenerative pathology of the central nervous system, mainly i... more Parkinson's disease (PD) is a neurodegenerative pathology of the central nervous system, mainly involving the selective and progressive loss of dopaminergic neurons from the substantia nigra, resulting in motor and non-motor symptoms. PD remains an incurable ailment; thus, treatments are limited to symptom alleviation. With long-term use, conventional treatments can become inefficient, often triggering possible side effects. Considering these drawbacks, drug discovery constantly turns to nature as a source of efficient therapeutics. Thus, this review explores animal venoms as a rich source of bioactive compounds with potent neuropharmacological profiles for the development of effective adjuvant treatments with fewer side effects, ultimately aiming for the neuroprotection of dopaminergic neurons and the symptomatic relief of PD.
Alzheimer's Disease (AD) is a progressive neurodegenerative disease that deeply affects patients,... more Alzheimer's Disease (AD) is a progressive neurodegenerative disease that deeply affects patients, their family and society. Although scientists have made intense efforts in seeking the cure for AD, no drug available today is able to stop AD progression. In this context, compounds isolated from animal venom are potentially successful drugs for neuroprotection, since they selectively bind to nervous system targets. In this review, we presented different studies using peptides isolated from animal venom for the treatment of AD. This is a growing field that will be very helpful in understanding and even curing neurodegenerative diseases, especially AD.
Chatergellus communis is a wasp species endemic to the neotropical region and its venom constitue... more Chatergellus communis is a wasp species endemic to the neotropical region and its venom constituents have never been described. In this study, two peptides from C. communis venom, denominated Communis and Communis-AAAA, were chemically and biologically characterized. In respect to the chemical characterization, the following amino acid sequences and molecular masses were identified: Communis: Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-COOH (1340.9Da) Communis-AAAA: Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-Ala-Ala-Ala-Ala-Val-Xle-NH2 (1836.3Da). Furthermore, their biological effects were compared, accounting for the differences in structural characteristics between the two peptides. To this end, three biological assays were performed in order to evaluate the hyperalgesic, edematogenic and hemolytic effects of these molecules. Communis-AAAA, unlike Communis, showed a potent hemolytic activity with EC50=142.6μM. Moreover, the highest dose of Communis-AAAA (2nmol/animal) ind...
Understanding the physiopathology of Alzheimer’s disease (AD) has improved substantially based on... more Understanding the physiopathology of Alzheimer’s disease (AD) has improved substantially based on studies of mouse models mimicking at least one aspect of the disease. Many transgenic lines have been established, leading to amyloidosis but lacking neurodegeneration. The aim of the current study was to generate a novel mouse model that develops neuritic plaques containing the aggressive pyroglutamate modified amyloid-β (pEAβ) species in the brain. The TAPS line was developed by intercrossing of the pEAβ-producing TBA2.1 mice with the plaque-developing line APPswe/PS1ΔE9. The phenotype of the new mouse line was characterized using immunostaining, and different cognitive and general behavioral tests. In comparison to the parental lines, TAPS animals developed an earlier onset of pathology and increased plaque load, including striatal pEAβ-positive neuritic plaques, and enhanced neuroinflammation. In addition to abnormalities in general behavior, locomotion, and exploratory behavior, TA...
Approximately 46.8 million people have been diagnosed worldwide with dementia, of which the most ... more 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. Considering that evolutionary pressure selected animal venom compounds that are very specific for a unique target, those can be a potential drug against AD. Octovespin was modified from occidentalin-1202, which is a peptide isolated from Polybia occidentalis wasp venom. In this context, this study evaluated the effect of treatment with octovespin against Amyloid-β (Aβ)-induced toxicity, which is postulated to be one of the main causes of AD, in both in vitro and in vivo tests. In vitro, octovespin was able to prevent Aβ aggregation in a ThT assay. In vivo, octovespin (0.15 nmol/animal) reverses memory impairment that is due to Aβ toxicity, in the Morris Water Maze and Novel Object Recognition Test. Our results suggested that octovespin is a potential drug for the treatment of AD, due to its ability to avoid Aβ aggregation in vitro and to prevent Aβ -induced memory deficit in mice.
The contribution of mouse models for basic and translational research at different levels is impo... more The contribution of mouse models for basic and translational research at different levels is important to understand neurodegenerative diseases, including tauopathies, by studying the alterations in the corresponding mouse models in detail. Moreover, several studies demonstrated that pathological as well as behavioral changes are influenced by the sex. For this purpose, we performed an in-depth characterization of the behavioral alterations in the transgenic Tau-P301L mouse model. Sex-matched wild type and homozygous Tau-P301L mice were tested in a battery of behavioral tests at different ages. Tau-P301L male mice showed olfactory and motor deficits as well as increased Tau pathology, which was not observed in Tau-P301L female mice. Both Tau-P301L male and female mice had phenotypic alterations in the SHIRPA test battery and cognitive deficits in the novel object recognition test. This study demonstrated that Tau-P301L mice have phenotypic alterations, which are in line with the his...
Multiple sources of evidence suggest that soluble amyloid β (Aβ)-oligomers are responsible for th... more Multiple sources of evidence suggest that soluble amyloid β (Aβ)-oligomers are responsible for the development and progression of Alzheimer’s disease (AD). In order to specifically eliminate these toxic Aβ-oligomers, our group has developed a variety of all-d-peptides over the past years. One of them, RD2, has been intensively studied and showed such convincing in vitro and in vivo properties that it is currently in clinical trials. In order to further optimize the compounds and to elucidate the characteristics of therapeutic d-peptides, several rational drug design approaches have been performed. Two of these d-peptides are the linear tandem (head-to-tail) d-peptide RD2D3 and its cyclized form cRD2D3. Tandemization and cyclization should result in an increased in vitro potency and increase pharmacokinetic properties, especially crossing the blood–brain-barrier. In comparison, cRD2D3 showed a superior pharmacokinetic profile to RD2D3. This fact suggests that higher efficacy can be a...
Besides a large variety of research on Alzheimer’s disease (AD), there are still open questions r... more Besides a large variety of research on Alzheimer’s disease (AD), there are still open questions regarding its pathophysiology. In this context, the development of a new transgenic mouse model TAPS, a genetic combination of heterozygous APP‐PS1dE9 and TBA2.1 mice, was accomplished. The TBA2.1 line expresses truncated amyloid‐β (Q3‐42), which is post‐translationally modified to pyroglutamate amyloid‐β (pE‐Aβ). Since this species of Aβ has been shown to be particularly cytotoxic and induces neurodegeneration in transgenic mice, TAPS mice were developed to mimic the combined human pathology of AD with amyloidosis and neurodegeneration.
Parkinson's disease (PD) is a neurodegenerative pathology of the central nervous system, mainly i... more Parkinson's disease (PD) is a neurodegenerative pathology of the central nervous system, mainly involving the selective and progressive loss of dopaminergic neurons from the substantia nigra, resulting in motor and non-motor symptoms. PD remains an incurable ailment; thus, treatments are limited to symptom alleviation. With long-term use, conventional treatments can become inefficient, often triggering possible side effects. Considering these drawbacks, drug discovery constantly turns to nature as a source of efficient therapeutics. Thus, this review explores animal venoms as a rich source of bioactive compounds with potent neuropharmacological profiles for the development of effective adjuvant treatments with fewer side effects, ultimately aiming for the neuroprotection of dopaminergic neurons and the symptomatic relief of PD.
Alzheimer's Disease (AD) is a progressive neurodegenerative disease that deeply affects patients,... more Alzheimer's Disease (AD) is a progressive neurodegenerative disease that deeply affects patients, their family and society. Although scientists have made intense efforts in seeking the cure for AD, no drug available today is able to stop AD progression. In this context, compounds isolated from animal venom are potentially successful drugs for neuroprotection, since they selectively bind to nervous system targets. In this review, we presented different studies using peptides isolated from animal venom for the treatment of AD. This is a growing field that will be very helpful in understanding and even curing neurodegenerative diseases, especially AD.
Chatergellus communis is a wasp species endemic to the neotropical region and its venom constitue... more Chatergellus communis is a wasp species endemic to the neotropical region and its venom constituents have never been described. In this study, two peptides from C. communis venom, denominated Communis and Communis-AAAA, were chemically and biologically characterized. In respect to the chemical characterization, the following amino acid sequences and molecular masses were identified: Communis: Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-COOH (1340.9Da) Communis-AAAA: Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-Ala-Ala-Ala-Ala-Val-Xle-NH2 (1836.3Da). Furthermore, their biological effects were compared, accounting for the differences in structural characteristics between the two peptides. To this end, three biological assays were performed in order to evaluate the hyperalgesic, edematogenic and hemolytic effects of these molecules. Communis-AAAA, unlike Communis, showed a potent hemolytic activity with EC50=142.6μM. Moreover, the highest dose of Communis-AAAA (2nmol/animal) ind...
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