4.7 Article

AmyP53, a Therapeutic Peptide Candidate for the Treatment of Alzheimer's and Parkinson's Disease: Safety, Stability, Pharmacokinetics Parameters and Nose-to Brain Delivery

Related references

Note: Only part of the references are listed.
Review Biochemistry & Molecular Biology

Effects of oligomer toxicity, fibril toxicity and fibril spreading in synucleinopathies

Roberta Cascella et al.

Summary: Protein misfolding is a common feature of protein deposition diseases, and soluble oligomeric species may be more toxic than fibrillar forms. Recent research shows that the beta-sheet core of aSyn fibrils cannot establish persistent interactions with lipid bilayers, but can release oligomeric species that cause immediate dysfunction. These oligomeric species can also contribute to pathogenesis through neuron-to-neuron spreading.

CELLULAR AND MOLECULAR LIFE SCIENCES (2022)

Review Biochemistry & Molecular Biology

Innovative treatment targeting gangliosides aimed at blocking the formation of neurotoxic alpha-synuclein oligomers in Parkinson's disease

Nouara Yahi et al.

Summary: Parkinson's disease is a major neurodegenerative disorder that requires a treatment targeting the root cause of the disease. This article highlights the role of lipid rafts in forming alpha-synuclein pore-like oligomers, which trigger a cascade of neurotoxic events, proposing blocking alpha-synuclein-ganglioside interactions as a potential therapeutic avenue for PD.

GLYCOCONJUGATE JOURNAL (2022)

Article Neurosciences

Lipid Rafts Act as a Common Platform for Amyloid-β Oligomer-Induced Alzheimer's Disease Pathology

Takeshi Kawarabayashi et al.

Summary: This study demonstrates that lipid rafts act as a common platform for the pathological cascades of AD.

JOURNAL OF ALZHEIMERS DISEASE (2022)

Review Biochemistry & Molecular Biology

Synaptic Disruption by Soluble Oligomers in Patients with Alzheimer's and Parkinson's Disease

Berenice A. Gutierrez et al.

Summary: Neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, result from the dysfunction and death of neurons. The presence of small soluble oligomers, such as amyloid beta and Tau oligomers in Alzheimer's, and alpha-synuclein oligomers in Parkinson's, is toxic and relevant to the development of these diseases. These oligomers increase during the early stages of pathology, leading to disruption of synaptic plasticity, synapse loss, inflammation, imbalance between excitatory and inhibitory transmission, and cognitive impairment. The absence of Tau oligomers at synapses in individuals with advanced Alzheimer's pathology but preserved cognition suggests that resilience mechanisms may depend on the interactions between soluble oligomers and their synaptic targets.

BIOMEDICINES (2022)

Review Pharmacology & Pharmacy

Development and Regulatory Challenges for Peptide Therapeutics

Doris Zane et al.

Summary: There is a growing interest in using peptide therapeutics to treat human diseases, despite the challenges in discovery, development, and delivery. The symposium discussed advancements in peptide therapeutics, toxicological considerations, regulatory perspectives, and the requirements for genotoxicity testing.

INTERNATIONAL JOURNAL OF TOXICOLOGY (2021)

Review Biochemistry & Molecular Biology

A Global Review on Short Peptides: Frontiers and Perspectives

Vasso Apostolopoulos et al.

Summary: Peptides, as fragments of proteins, play vital roles in biological processes with unique characteristics and promising potentials in biotherapies. Current research focuses on short peptide-based therapeutic developments, covering disease treatments, biosynthesis, nanotechnology, peptide limitations overcoming, among others.

MOLECULES (2021)

Article Biochemistry & Molecular Biology

Gene Therapy Strategy for Alzheimer's and Parkinson's Diseases Aimed at Preventing the Formation of Neurotoxic Oligomers in SH-SY5Y Cells

Assou El-Battari et al.

Summary: The study introduces a gene therapy approach to prevent the formation of neurotoxic oligomers by targeting brain gangliosides, representing a new strategy for treating Alzheimer's and Parkinson's diseases. By genetically modifying brain cells to secrete a therapeutic peptide inhibitor, the therapy effectively blocks the initial steps of neurodegeneration cascade and provides specific protection against oligomer formation. The results demonstrate the potential of this unique gene therapy approach in treating major neurodegenerative disorders.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Endocrinology & Metabolism

Intranasal Administration of PACAP Is an Efficient Delivery Route to Reduce Infarct Volume and Promote Functional Recovery After Transient and Permanent Middle Cerebral Artery Occlusion

Asma Cherait et al.

Summary: Intranasal administration of pituitary adenylate cyclase-activating polypeptide (PACAP) is more efficient in reducing infarct volume and improving functional recovery compared to intravenous and intraperitoneal administration, showing significant neuroprotective effects in C57BL/6 mice after transient or permanent middle cerebral artery occlusion (MCAO).

FRONTIERS IN ENDOCRINOLOGY (2021)

Article Medicine, General & Internal

Donanemab in Early Alzheimer's Disease

Mark A. Mintun et al.

Summary: In this study, donanemab showed improved composite scores for cognition and daily living activities compared to placebo in patients with early Alzheimer's disease at 76 weeks, although secondary outcomes varied. Longer and larger trials are needed to further explore the efficacy and safety of donanemab in Alzheimer's disease.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Article Neurosciences

Prediction of Transmembrane Regions, Cholesterol, and Ganglioside Binding Sites in Amyloid-Forming Proteins Indicate Potential for Amyloid Pore Formation

Katja Venko et al.

Summary: Besides amyloid fibrils, amyloid pores (APs) are another mechanism of amyloid-induced toxicity. Predictive methods were used to assess 30 amyloid-forming proteins (AFPs) for their propensity to form transmembrane channels, providing insights for future experiments towards a deeper understanding of amyloid toxicity. The presence of transmembrane (TM) regions, cholesterol (CBM), and ganglioside binding motifs (GBM) in pathological AFPs suggest their potential for pore formation.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2021)

Review Cell Biology

Membrane Interactions and Toxicity by Misfolded Protein Oligomers

Mario Gonzalez-Garcia et al.

Summary: The conversion of soluble proteins into insoluble amyloid aggregates is linked to various neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. The small prefibrillar oligomers formed during protein aggregation are identified as the most harmful species. Interactions with biological membranes play a crucial role in the onset of cellular toxicity. Further research is needed to understand the transient interactions involving heterogeneous protein aggregates for developing effective therapeutic strategies against protein misfolding diseases.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

Review Biochemistry & Molecular Biology

Neurotoxic Soluble Amyloid Oligomers Drive Alzheimer's Pathogenesis and Represent a Clinically Validated Target for Slowing Disease Progression

Martin Tolar et al.

Summary: Research shows that inhibiting the toxicity of Aβ oligomers is an effective approach to slow or stop the progression of Alzheimer's disease, with drugs targeting other Aβ species failing to show clinical effects, while those with the APOE4 allele are more likely to benefit.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Chemistry, Physical

Insights into Structure and Aggregation Behavior of Elastin-like Polypeptide Coacervates: All-Atom Molecular Dynamics Simulations

Nan K. Li et al.

Summary: The stimuli-responsive character of elastin-like polypeptides (ELP) has led to their use in a wide range of applications. The temperature-triggered aggregation of ELPs is a complex phenomenon with differences observed in thermal hysteresis between sequences. Overall, this study provides insights into the sequence-dependent structure of ELP coacervates and the molecular behavior of individual peptides during aggregation.

JOURNAL OF PHYSICAL CHEMISTRY B (2021)

Review Neurosciences

The biological pathways of Alzheimer disease: a review

Marco Calabro et al.

Summary: Alzheimer's disease is a progressive neurodegenerative disorder that mainly affects older individuals, with a rapidly increasing number of cases worldwide. The exact molecular events and biological pathways underlying the disease are still unknown, despite research on its biological and genetic components.

AIMS NEUROSCIENCE (2021)

Article Clinical Neurology

Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019

David S. Knopman et al.

Summary: Aducanumab recently underwent two large phase III clinical trials that were stopped prematurely by the sponsor due to divergent outcomes. One trial showed potential benefits from high doses of Aducanumab, while the other did not show any benefits. Further analysis is needed to determine the true efficacy as a treatment for Alzheimer's disease.

ALZHEIMERS & DEMENTIA (2021)

Review Biochemistry & Molecular Biology

Aβ-ganglioside interactions in the pathogenesis of Alzheimer's disease

Katsumi Matsuzaki

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES (2020)

Review Biochemistry & Molecular Biology

Evolving a Peptide: Library Platforms and Diversification Strategies

Kristof Bozovicar et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Review Medicine, General & Internal

Diagnosis and Treatment of Parkinson Disease A Review

Melissa J. Armstrong et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2020)

Review Biochemistry & Molecular Biology

The Toxicity and Polymorphism of β-Amyloid Oligomers

Ya-ru Huang et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Article Multidisciplinary Sciences

Unroofing site-specific alpha-synuclein-lipid interactions at the plasma membrane

Upneet Kaur et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

Review Biochemistry & Molecular Biology

Progress toward Alzheimer's disease treatment: Leveraging the Achilles' heel of Aβ oligomers?

Jacques Fantini et al.

PROTEIN SCIENCE (2020)

Review Neurosciences

Models of the blood-brain barrier using iPSC-derived cells

Louise Delsing et al.

MOLECULAR AND CELLULAR NEUROSCIENCE (2020)

Review Neurosciences

Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications

Simonetta Sipione et al.

FRONTIERS IN NEUROSCIENCE (2020)

Review Biochemistry & Molecular Biology

Sequence and structure-based peptides as potent amyloid inhibitors: A review

Amit Mitra et al.

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS (2020)

Review Biochemistry & Molecular Biology

Liraglutide and its Neuroprotective PropertiesFocus on Possible Biochemical Mechanisms in Alzheimer's Disease and Cerebral Ischemic Events

Michal Wicinski et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

Review Biochemistry & Molecular Biology

A Comprehensive Review on Current Advances in Peptide Drug Development and Design

Andy Chi-Lung Lee et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

Article Neurosciences

Intraneuronal Tau Misfolding Induced by Extracellular Amyloid-β Oligomers

Lauren K. Rudenko et al.

JOURNAL OF ALZHEIMERS DISEASE (2019)

Article Biochemistry & Molecular Biology

GM1 Ganglioside role in the interaction of Alpha-synuclein with lipid membranes: Morphology and structure

F. Perissinotto et al.

BIOPHYSICAL CHEMISTRY (2019)

Article Biochemistry & Molecular Biology

Therapeutic peptides for CNS indications: Progress and challenges

Bruce H. Morimoto

BIOORGANIC & MEDICINAL CHEMISTRY (2018)

Review Neurosciences

The Amyloid-beta Oligomer Hypothesis: Beginning of the Third Decade

Erika N. Cline et al.

JOURNAL OF ALZHEIMERS DISEASE (2018)

Review Chemistry, Multidisciplinary

Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs

Mukta Agrawal et al.

JOURNAL OF CONTROLLED RELEASE (2018)

Review Biochemistry & Molecular Biology

Peptides as Potential Therapeutics for Alzheimer's Disease

Samo Ribaric

MOLECULES (2018)

Review Clinical Neurology

Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

Melanie D. Sweeney et al.

NATURE REVIEWS NEUROLOGY (2018)

Review Medicine, Research & Experimental

Cell penetrating peptides: A concise review with emphasis on biomedical applications

Hossein Derakhshankhah et al.

BIOMEDICINE & PHARMACOTHERAPY (2018)

Editorial Material Multidisciplinary Sciences

THE AMYLOID HYPOTHESIS ON TRAIL

Simon Makin

NATURE (2018)

Review Neurosciences

Evaluation of intranasal delivery route of drug administration for brain targeting

Franciska Erdo et al.

BRAIN RESEARCH BULLETIN (2018)

Article Cell Biology

Spatial Relationship and Functional Relevance of Three Lipid Domain Populations at the Erythrocyte Surface

Louise Conrard et al.

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY (2018)

Article Biochemistry & Molecular Biology

Ion Channel Formation by Amyloid-β42 Oligomers but Not Amyloid-β40 in Cellular Membranes

David C. Bode et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2017)

Article Multidisciplinary Sciences

THPdb: Database of FDA-approved peptide and protein therapeutics

Salman Sadullah Usmani et al.

PLOS ONE (2017)

Article Biochemistry & Molecular Biology

Role of membrane GM1 on early neuronal membrane actions of Aβ during onset of Alzheimer's disease

E. J. Fernandez-Perez et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE (2017)

Review Clinical Neurology

Alpha-synuclein oligomers: a new hope

Nora Bengoa-Vergniory et al.

ACTA NEUROPATHOLOGICA (2017)

Article Biochemistry & Molecular Biology

Alpha-Synuclein Oligomers Interact with Metal Ions to Induce Oxidative Stress and Neuronal Death in Parkinson's Disease

Emma Deas et al.

ANTIOXIDANTS & REDOX SIGNALING (2016)

Article Biochemistry & Molecular Biology

Prediction of cell-penetrating peptides with feature selection techniques

Hua Tang et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2016)

Article Biochemistry & Molecular Biology

Broad neutralization of calcium-permeable amyloid pore channels with a chimeric Alzheimer/Parkinson peptide targeting brain gangliosides

Coralie Di Scala et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE (2016)

Review Biochemistry & Molecular Biology

Gangliosides of the Vertebrate Nervous System

Ronald L. Schnaar

JOURNAL OF MOLECULAR BIOLOGY (2016)

Article Multidisciplinary Sciences

Common molecular mechanism of amyloid pore formation by Alzheimer's β-amyloid peptide and α-synuclein

Coralie Di Scala et al.

SCIENTIFIC REPORTS (2016)

Review Pharmacology & Pharmacy

Intranasal Delivery of Proteins and Peptides in the Treatment of Neurodegenerative Diseases

M. Elizabeth Meredith et al.

AAPS JOURNAL (2015)

Review Biochemistry & Molecular Biology

GM1 ganglioside and Alzheimer's disease

Katsuhiko Yanagisawa

GLYCOCONJUGATE JOURNAL (2015)

Review Chemistry, Multidisciplinary

Cell-Penetrating Peptides: Design, Synthesis, and Applications

Dana Maria Copolovici et al.

ACS NANO (2014)

Review Pharmacology & Pharmacy

Blood-brain barrier models and their relevance for a successful development of CNS drug delivery systems: A review

Joana Bicker et al.

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS (2014)

Review Chemistry, Multidisciplinary

Quantitative analysis of drug delivery to the brain via nasal route

Luba Kozlovskaya et al.

JOURNAL OF CONTROLLED RELEASE (2014)

Review Neurosciences

Oligomeric Aβ-induced synaptic dysfunction in Alzheimer's disease

Shichun Tu et al.

MOLECULAR NEURODEGENERATION (2014)

Review Clinical Neurology

Targeting the proper amyloid-beta neuronal toxins: a path forward for Alzheimer's disease immunotherapeutics

William F. Goure et al.

ALZHEIMERS RESEARCH & THERAPY (2014)

Article Clinical Neurology

Amyloid-Beta Oligomerization in Alzheimer Dementia versus High-Pathology Controls

Thomas J. Esparza et al.

ANNALS OF NEUROLOGY (2013)

Article Chemistry, Physical

Alzheimer's disease: which type of amyloid-preventing drug agents to employ?

Hyunbum Jang et al.

PHYSICAL CHEMISTRY CHEMICAL PHYSICS (2013)

Editorial Material Physiology

Alzheimer's disease (AD) as a disorder of the plasma membrane

Walter J. Lukiw

FRONTIERS IN PHYSIOLOGY (2013)

Article Biochemistry & Molecular Biology

Effect of intranasal arginine vasopressin on human headache

Jun Yang et al.

PEPTIDES (2012)

Article Biochemistry & Molecular Biology

Molecular Basis for the Glycosphingolipid-Binding Specificity of α-Synuclein: Key Role of Tyrosine 39 in Membrane Insertion

Jacques Fantini et al.

JOURNAL OF MOLECULAR BIOLOGY (2011)

Article Multidisciplinary Sciences

In vivo demonstration that α-synuclein oligomers are toxic

Beate Winner et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2011)

Article Computer Science, Interdisciplinary Applications

PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel

Yong Zhang et al.

COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE (2010)

Article Multidisciplinary Sciences

Truncated β-amyloid peptide channels provide an alternative mechanism for Alzheimer's Disease and Down syndrome

Hyunbum Jang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2010)

Article Biochemistry & Molecular Biology

Annular Protofibrils Are a Structurally and Functionally Distinct Type of Amyloid Oligomer

Rakez Kayed et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2009)

Article Chemistry, Multidisciplinary

A New Minimal-Stress Freely-Moving Rat Model for Preclinical Studies on Intranasal Administration of CNS Drugs

Jasper Stevens et al.

PHARMACEUTICAL RESEARCH (2009)

Article Clinical Neurology

A new amyloid μ variant favoring oligomerization in Alzheimer's-type dementia

Takami Tomiyama et al.

ANNALS OF NEUROLOGY (2008)

Article Biochemistry & Molecular Biology

Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory

Ganesh M. Shankar et al.

NATURE MEDICINE (2008)

Article Geriatrics & Gerontology

Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers

Fernanda G. De Felice et al.

NEUROBIOLOGY OF AGING (2008)

Article Biochemistry & Molecular Biology

The binding constant for amyloid Aβ40 peptide interaction with human serum albumin

Malgorzata Rozga et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2007)

Article Endocrinology & Metabolism

Metabolism of cydiastatin 4 and analogues by enzymes associated with the midgut and haemolymph of Manduca sexta larvae

Neil Audsley et al.

GENERAL AND COMPARATIVE ENDOCRINOLOGY (2007)

Article Clinical Neurology

G2019S LRRK2 mutation causing Parkinson's disease without Lewy bodies

Carles Gaig et al.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2007)

Review Cell Biology

Soluble protein oligomers in neurodegeneration:: lessons from the Alzheimer's amyloid β-peptide

Christian Haass et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2007)

Article Multidisciplinary Sciences

Intranasal administration of nerve growth factor (NGF) rescues recognition memory deficits in AD11 anti-NGF transgenic mice

R De Rosa et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2005)

Article Clinical Neurology

alpha-Synuclein pathology does not predict extrapyramidal symptoms or dementia

L Parkkinen et al.

ANNALS OF NEUROLOGY (2005)

Article Pharmacology & Pharmacy

Human intestinal absorption of imidacloprid with Caco-2 cells as enterocyte model

JL Brunet et al.

TOXICOLOGY AND APPLIED PHARMACOLOGY (2004)

Article Chemistry, Medicinal

In vitro analysis of stable, receptor-selective neurotensin[8-13] analogues

KP Kokko et al.

JOURNAL OF MEDICINAL CHEMISTRY (2003)

Article Clinical Neurology

Lewy body cortical involvement may not always predict dementia in Parkinson's disease

C Colosimo et al.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2003)

Article Biochemistry & Molecular Biology

Pharmacological profiles of peptide drug candidates for the treatment of Alzheimer's disease

C Adessi et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2003)

Article Multidisciplinary Sciences

Neurodegenerative disease - Amyloid pores from pathogenic mutations

HA Lashuel et al.

NATURE (2002)