scholarly journals Animal models in neurodegenerative diseases

Author(s):  
E. C. Hirsch
2021 ◽  
Vol 16 ◽  
pp. 263310552110187
Author(s):  
Christopher D Link

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.”


2021 ◽  
Vol 22 (15) ◽  
pp. 8196
Author(s):  
Dorit Trudler ◽  
Swagata Ghatak ◽  
Stuart A. Lipton

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.


2016 ◽  
Vol 53 (2) ◽  
pp. 327-348 ◽  
Author(s):  
S. A. Youssef ◽  
M. T. Capucchio ◽  
J. E. Rofina ◽  
J. K. Chambers ◽  
K. Uchida ◽  
...  

2015 ◽  
Vol 6 (5-6) ◽  
pp. 361-382 ◽  
Author(s):  
Sheila Leone ◽  
Giorgio Noera ◽  
Alfio Bertolini

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.


2021 ◽  
Author(s):  
Daniel Palenzuela Gardon ◽  
Majel Cervantes Llano ◽  
Beatriz Piniella Matamoros ◽  
Hanlet Camacho Rodriguez ◽  
Chan-yuan Tan ◽  
...  

2019 ◽  
Vol 59 (1) ◽  
pp. 237-261 ◽  
Author(s):  
Miguel Moutinho ◽  
Juan F. Codocedo ◽  
Shweta S. Puntambekar ◽  
Gary E. Landreth

Neurodegenerative diseases are characterized by a progressive loss of neurons that leads to a broad range of disabilities, including severe cognitive decline and motor impairment, for which there are no effective therapies. Several lines of evidence support a putative therapeutic role of nuclear receptors (NRs) in these types of disorders. NRs are ligand-activated transcription factors that regulate the expression of a wide range of genes linked to metabolism and inflammation. Although the activation of NRs in animal models of neurodegenerative disease exhibits promising results, the translation of this strategy to clinical practice has been unsuccessful. In this review we discuss the role of NRs in neurodegenerative diseases in light of preclinical and clinical studies, as well as new findings derived from the analysis of transcriptomic databases from humans and animal models. We discuss the failure in the translation of NR-based therapeutic approaches and consider alternative and novel research avenues in the development of effective therapies for neurodegenerative diseases.


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