BOOK REVIEWS: Neuromethods 21: Animal Models of Neurological Disease, 1 Neurodegenerative Diseases.

Numerous studies have identified microbial sequences or epitopes in pathological and non-pathological human brain samples. It has not been resolved if these observations are artifactual, or truly represent population of the brain by microbes. Given the tempting speculation that resident microbes could play a role in the many neuropsychiatric and neurodegenerative diseases that currently lack clear etiologies, there is a strong motivation to determine the “ground truth” of microbial existence in living brains. Here I argue that the evidence for the presence of microbes in diseased brains is quite strong, but a compelling demonstration of resident microbes in the healthy human brain remains to be done. Dedicated animal models studies may be required to determine if there is indeed a “brain microbiome.”

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Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22158196 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8196

Author(s):

Dorit Trudler ◽

Swagata Ghatak ◽

Stuart A. Lipton

Keyword(s):

Drug Discovery ◽

Animal Models ◽

Neurodegenerative Diseases ◽

Disease Modeling ◽

Induced Pluripotent Stem Cell ◽

Neural Function ◽

Neural Cells ◽

Human Samples ◽

Healthy Donors ◽

Induced Pluripotent

Neurodegenerative diseases affect millions of people worldwide and are characterized by the chronic and progressive deterioration of neural function. Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), represent a huge social and economic burden due to increasing prevalence in our aging society, severity of symptoms, and lack of effective disease-modifying therapies. This lack of effective treatments is partly due to a lack of reliable models. Modeling neurodegenerative diseases is difficult because of poor access to human samples (restricted in general to postmortem tissue) and limited knowledge of disease mechanisms in a human context. Animal models play an instrumental role in understanding these diseases but fail to comprehensively represent the full extent of disease due to critical differences between humans and other mammals. The advent of human-induced pluripotent stem cell (hiPSC) technology presents an advantageous system that complements animal models of neurodegenerative diseases. Coupled with advances in gene-editing technologies, hiPSC-derived neural cells from patients and healthy donors now allow disease modeling using human samples that can be used for drug discovery.

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Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases

Veterinary Pathology ◽

10.1177/0300985815623997 ◽

2016 ◽

Vol 53 (2) ◽

pp. 327-348 ◽

Cited By ~ 47

Author(s):

S. A. Youssef ◽

M. T. Capucchio ◽

J. E. Rofina ◽

J. K. Chambers ◽

K. Uchida ◽

...

Keyword(s):

Animal Models ◽

Neurodegenerative Diseases ◽

Laboratory Animals ◽

Aging Brain

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Developments and new vistas in the field of melanocortins

BioMolecular Concepts ◽

10.1515/bmc-2015-0023 ◽

2015 ◽

Vol 6 (5-6) ◽

pp. 361-382 ◽

Cited By ~ 4

Author(s):

Sheila Leone ◽

Giorgio Noera ◽

Alfio Bertolini

Keyword(s):

Animal Models ◽

Neurodegenerative Diseases ◽

Sexual Activity ◽

Ischemia Reperfusion ◽

Gouty Arthritis ◽

Traumatic Injury ◽

Large Body ◽

Hypovolemic Shock ◽

Therapeutic Effects ◽

Tissue Ischemia

AbstractMelanocortins play a fundamental role in several basic functions of the organism (sexual activity, feeding, inflammation and immune responses, pain sensitivity, response to stressful situations, motivation, attention, learning, and memory). Moreover, a large body of animal data, some of which were also confirmed in humans, unequivocally show that melanocortins also have impressive therapeutic effects in several pathological conditions that are the leading cause of mortality and disability worldwide (hemorrhagic, or anyway hypovolemic, shock; septic shock; respiratory arrest; cardiac arrest; ischemia- and ischemia/reperfusion-induced damage of the brain, heart, intestine, and other organs; traumatic injury of brain, spinal cord, and peripheral nerves; neuropathic pain; toxic neuropathies; gouty arthritis; etc.). Recent data obtained in animal models seem to moreover confirm previous hypotheses and preliminary data concerning the neurotrophic activity of melanocortins in neurodegenerative diseases, in particular Alzheimer’s disease. Our aim was (i) to critically reconsider the established extrahormonal effects of melanocortins (on sexual activity, feeding, inflammation, tissue hypoperfusion, and traumatic damage of central and peripheral nervous system) at the light of recent findings, (ii) to review the most recent advancements, particularly on the effects of melanocortins in models of neurodegenerative diseases, (iii) to discuss the reasons that support the introduction into clinical practice of melanocortins as life-saving agents in shock conditions and that suggest to verify in clinical setting the impressive results steadily obtained with melanocortins in different animal models of tissue ischemia and ischemia/reperfusion, and finally, (iv) to mention the advisable developments, particularly in terms of selectivity of action and of effects.

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Mechanisms of neuronal death in disease: defining the models and the players

Biochemical Journal ◽

10.1042/bj20081118 ◽

2008 ◽

Vol 415 (2) ◽

pp. 165-182 ◽

Cited By ~ 61

Author(s):

Elena M. Ribe ◽

Esther Serrano-Saiz ◽

Nsikan Akpan ◽

Carol M. Troy

Keyword(s):

Neurodegenerative Diseases ◽

Neuronal Death ◽

Neurological Disease ◽

Neurodegenerative Disorder ◽

Cellular Level ◽

Therapeutic Interventions ◽

Common Cause ◽

Life And Death ◽

Caspase Family ◽

Common Neurodegenerative Disorder

Dysregulation of life and death at the cellular level leads to a variety of diseases. In the nervous system, aberrant neuronal death is an outstanding feature of neurodegenerative diseases. Since the discovery of the caspase family of proteases, much effort has been made to determine how caspases function in disease, including neurodegenerative diseases. Although many papers have been published examining caspases in neuronal death and disease, the pathways have not been fully clarified. In the present review, we examine the potential players in the death pathways, the current tools for examining these players and the models for studying neurological disease. Alzheimer's disease, the most common neurodegenerative disorder, and cerebral ischaemia, the most common cause of neurological death, are used to illustrate our current understanding of death signalling in neurodegenerative diseases. A better understanding of the neuronal death pathways would provide targets for the development of therapeutic interventions for these diseases.

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