scholarly journals Phytocannabinoids: General Aspects and Pharmacological Potential in Neurodegenerative Diseases

2020 ◽  
Vol 18 ◽  
Author(s):  
Graziella dos Reis Franco ◽  
Scott Smid ◽  
Cláudio Viegas
Keyword(s):  
Drug Development ◽  
Neurodegenerative Diseases ◽  
Disease Progression ◽  
Potential Application ◽  
Neurological Diseases ◽  
Drug Candidates ◽  
Disease Modifying ◽  
Pharmacological Potential ◽  
General Aspects ◽  
State Of Art

: In the last few years research into Cannabis and its constituent phytocannabinoids has burgeoned, particularly in the potential application of novel cannabis phytochemicals for the treatment of diverse illnesses related to neurodegeneration and dementia, including Alzheimer's (AD), Parkinson's (PD) and Huntington's disease (HD). To date, these neurological diseases have mostly relied on symptomatological management. However, with an aging population globally, the search for more efficient and disease-modifying treatments that could delay or mitigate disease progression is imperative. In this context, this review aims to present a state of art in the research with cannabinoids and novel cannabinoid-based drug candidates that have been emerged as novel promising alternatives for drug development and innovation in the therapeutics of a number of diseases, especially those related to CNS-disturbance and impairment.

scholarly journals Repurposing Drugs to Treat Heart and Brain Illness

2021 ◽  
Vol 14 (6) ◽  
pp. 573
Author(s):  
Maranda S. Cantrell ◽  
Alejandro Soto-Avellaneda ◽  
Jackson D. Wall ◽  
Aaron D. Ajeti ◽  
Brad E. Morrison ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Neurodegenerative Diseases ◽  
Disease Progression ◽  
Drug Repurposing ◽  
Pharmacological Treatments ◽  
Representative Case ◽  
Inflammatory Processes ◽  
Expensive Process ◽  
Selection Of

Drug development is a complicated, slow and expensive process with high failure rates. One strategy to mitigate these factors is to recycle existing drugs with viable safety profiles and have gained Food and Drug Administration approval following extensive clinical trials. Cardiovascular and neurodegenerative diseases are difficult to treat, and there exist few effective therapeutics, necessitating the development of new, more efficacious drugs. Recent scientific studies have led to a mechanistic understanding of heart and brain disease progression, which has led researchers to assess myriad drugs for their potential as pharmacological treatments for these ailments. The focus of this review is to survey strategies for the selection of drug repurposing candidates and provide representative case studies where drug repurposing strategies were used to discover therapeutics for cardiovascular and neurodegenerative diseases, with a focus on anti-inflammatory processes where new drug alternatives are needed.

Biobanking for Neurodegenerative Diseases: Challenge for Translational Research and Data Privacy

2021 ◽  
pp. 107385842110366
Author(s):  
Emilia Giannella ◽  
Valentino Notarangelo ◽  
Caterina Motta ◽  
Giulia Sancesario
Keyword(s):  
Neurodegenerative Diseases ◽  
Translational Research ◽  
Data Protection ◽  
Biological Samples ◽  
Data Privacy ◽  
Neurological Diseases ◽  
Great Effort ◽  
General Data Protection Regulation ◽  
In Silico Studies

Biobanking has emerged as a strategic challenge to promote knowledge on neurological diseases, by the application of translational research. Due to the inaccessibility of the central nervous system, the advent of biobanks, as structure collecting biospecimens and associated data, are essential to turn experimental results into clinical practice. Findings from basic research, omics sciences, and in silico studies, definitely require validation in clinically well-defined cohorts of patients, even more valuable when longitudinal, or including preclinical and asymptomatic individuals. Finally, collecting biological samples requires a great effort to guarantee respect for transparency and protection of sensitive data of patients and donors. Since the European General Data Protection Regulation 2016/679 has been approved, concerns about the use of data in biomedical research have emerged. In this narrative review, we focus on the essential role of biobanking for translational research on neurodegenerative diseases. Moreover, we address considerations for biological samples and data collection, the importance of standardization in the preanalytical phase, data protection (ethical and legal) and the role of donors in improving research in this field.

scholarly journals Molecular mechanisms of cell death in neurological diseases

2021 ◽  
Author(s):  
Diane Moujalled ◽  
Andreas Strasser ◽  
Jeffrey R. Liddell
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
Neurological Diseases ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Response To Therapy ◽  
Signalling Cascades ◽  
The Brain

AbstractTightly orchestrated programmed cell death (PCD) signalling events occur during normal neuronal development in a spatially and temporally restricted manner to establish the neural architecture and shaping the CNS. Abnormalities in PCD signalling cascades, such as apoptosis, necroptosis, pyroptosis, ferroptosis, and cell death associated with autophagy as well as in unprogrammed necrosis can be observed in the pathogenesis of various neurological diseases. These cell deaths can be activated in response to various forms of cellular stress (exerted by intracellular or extracellular stimuli) and inflammatory processes. Aberrant activation of PCD pathways is a common feature in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, resulting in unwanted loss of neuronal cells and function. Conversely, inactivation of PCD is thought to contribute to the development of brain cancers and to impact their response to therapy. For many neurodegenerative diseases and brain cancers current treatment strategies have only modest effect, engendering the need for investigations into the origins of these diseases. With many diseases of the brain displaying aberrations in PCD pathways, it appears that agents that can either inhibit or induce PCD may be critical components of future therapeutic strategies. The development of such therapies will have to be guided by preclinical studies in animal models that faithfully mimic the human disease. In this review, we briefly describe PCD and unprogrammed cell death processes and the roles they play in contributing to neurodegenerative diseases or tumorigenesis in the brain. We also discuss the interplay between distinct cell death signalling cascades and disease pathogenesis and describe pharmacological agents targeting key players in the cell death signalling pathways that have progressed through to clinical trials.

scholarly journals Mechanisms of Intranasal Deferoxamine in Neurodegenerative and Neurovascular Disease

2021 ◽  
Vol 14 (2) ◽  
pp. 95
Author(s):  
Jacob Kosyakovsky ◽  
Jared Fine ◽  
William Frey ◽  
Leah Hanson
Keyword(s):  
Targeted Delivery ◽  
Cognitive Aging ◽  
Brain Aging ◽  
Neurological Diseases ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Modern Medicine ◽  
Potential Applicability ◽  
Disease Modifying ◽  
Further Development

Identifying disease-modifying therapies for neurological diseases remains one of the greatest gaps in modern medicine. Herein, we present the rationale for intranasal (IN) delivery of deferoxamine (DFO), a high-affinity iron chelator, as a treatment for neurodegenerative and neurovascular disease with a focus on its novel mechanisms. Brain iron dyshomeostasis with iron accumulation is a known feature of brain aging and is implicated in the pathogenesis of a number of neurological diseases. A substantial body of preclinical evidence and early clinical data has demonstrated that IN DFO and other iron chelators have strong disease-modifying impacts in Alzheimer’s disease (AD), Parkinson’s disease (PD), ischemic stroke, and intracranial hemorrhage (ICH). Acting by the disease-nonspecific pathway of iron chelation, DFO targets each of these complex diseases via multifactorial mechanisms. Accumulating lines of evidence suggest further mechanisms by which IN DFO may also be beneficial in cognitive aging, multiple sclerosis, traumatic brain injury, other neurodegenerative diseases, and vascular dementia. Considering its known safety profile, targeted delivery method, robust preclinical efficacy, multiple mechanisms, and potential applicability across many neurological diseases, the case for further development of IN DFO is considerable.

scholarly journals Role of Neuroglobin in the Neuroprotective Actions of Estradiol and Estrogenic Compounds

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1907
Author(s):  
George E. Barreto ◽  
Andrew J. McGovern ◽  
Luis M. Garcia-Segura
Keyword(s):  
Sex Differences ◽  
Signaling Pathways ◽  
Glial Cell ◽  
Potential Application ◽  
Neurological Diseases ◽  
Brain Pathology ◽  
Synthetic Steroids ◽  
Neuroprotective Actions ◽  
Estrogenic Regulation

Estradiol exerts neuroprotective actions that are mediated by the regulation of a variety of signaling pathways and homeostatic molecules. Among these is neuroglobin, which is upregulated by estradiol and translocated to the mitochondria to sustain neuronal and glial cell adaptation to injury. In this paper, we will discuss the role of neuroglobin in the neuroprotective mechanisms elicited by estradiol acting on neurons, astrocytes and microglia. We will also consider the role of neuroglobin in the neuroprotective actions of clinically relevant synthetic steroids, such as tibolone. Finally, the possible contribution of the estrogenic regulation of neuroglobin to the generation of sex differences in brain pathology and the potential application of neuroglobin as therapy against neurological diseases will be examined.

scholarly journals A Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 34
Author(s):  
Kohei Segawa ◽  
Yukari Blumenthal ◽  
Yuki Yamawaki ◽  
Gen Ohtsuki
Keyword(s):  
Neurodegenerative Diseases ◽  
Lymphatic System ◽  
Psychiatric Symptoms ◽  
Neurological Diseases ◽  
Immune Surveillance ◽  
Brain Network ◽  
Cellular Mechanisms ◽  
Postmortem Brains ◽  
New Interpretation ◽  
The Brain

The lymphatic system is important for antigen presentation and immune surveillance. The lymphatic system in the brain was originally introduced by Giovanni Mascagni in 1787, while the rediscovery of it by Jonathan Kipnis and Kari Kustaa Alitalo now opens the door for a new interpretation of neurological diseases and therapeutic applications. The glymphatic system for the exchanges of cerebrospinal fluid (CSF) and interstitial fluid (ISF) is associated with the blood-brain barrier (BBB), which is involved in the maintenance of immune privilege and homeostasis in the brain. Recent notions from studies of postmortem brains and clinical studies of neurodegenerative diseases, infection, and cerebral hemorrhage, implied that the breakdown of those barrier systems and infiltration of activated immune cells disrupt the function of both neurons and glia in the parenchyma (e.g., modulation of neurophysiological properties and maturation of myelination), which causes the abnormality in the functional connectivity of the entire brain network. Due to the vulnerability, such dysfunction may occur in developing brains as well as in senile or neurodegenerative diseases and may raise the risk of emergence of psychosis symptoms. Here, we introduce this hypothesis with a series of studies and cellular mechanisms.

Coalition Against Major Diseases: Precompetitive Collaborations and Regulatory Paths to Accelerating Drug Development for Neurodegenerative Diseases

2013 ◽  
Vol 47 (6) ◽  
pp. 632-638 ◽  
Author(s):  
Diane Stephenson ◽  
Enrique Aviles ◽  
Lisa J. Bain ◽  
Martha Brumfield ◽  
Maria Carrillo ◽  
...  
Keyword(s):  
Drug Development ◽  
Neurodegenerative Diseases

scholarly journals Astrocytic transporters in Alzheimer's disease

2017 ◽  
Vol 474 (3) ◽  
pp. 333-355 ◽  
Author(s):  
Chris Ugbode ◽  
Yuhan Hu ◽  
Benjamin Whalley ◽  
Chris Peers ◽  
Marcus Rattray ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Neurological Diseases ◽  
Current Evidence ◽  
Specific Targeting ◽  
Disease Modifying Therapies ◽  
The Central Nervous System ◽  
Disease Modifying ◽  
And Function

Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both cellular and molecular changes at an early stage in neurological diseases, including Alzheimer's disease (AD). These changes may reflect a change from a neuroprotective to a neurotoxic phenotype. Given the lack of current disease-modifying therapies for AD, astrocytes have become an interesting and viable target for therapeutic intervention. The astrocyte transport system covers a diverse array of proteins involved in metabolic support, neurotransmission and synaptic architecture. Therefore, specific targeting of individual transporter families has the potential to suppress neurodegeneration, a characteristic hallmark of AD. A small number of the 400 transporter superfamilies are expressed in astrocytes, with evidence highlighting a fraction of these are implicated in AD. Here, we review the current evidence for six astrocytic transporter subfamilies involved in AD, as reported in both animal and human studies. This review confirms that astrocytes are indeed a viable target, highlights the complexities of studying astrocytes and provides future directives to exploit the potential of astrocytes in tackling AD.

scholarly journals Discovery Methodology of Novel Conotoxins from Conus Species

Marine Drugs ◽  
2018 ◽  
Vol 16 (11) ◽  
pp. 417 ◽  
Author(s):  
Ying Fu ◽  
Cheng Li ◽  
Shuai Dong ◽  
Yong Wu ◽  
Dongting Zhangsun ◽  
...  
Keyword(s):  
Drug Development ◽  
Gene Cloning ◽  
High Throughput ◽  
Disulfide Bond ◽  
Cone Snail ◽  
Crude Venom ◽  
Drug Candidates ◽  
Conus Species ◽  
New Drug Development ◽  
Natural Peptides

Cone snail venoms provide an ideal resource for neuropharmacological tools and drug candidates discovery, which have become a research hotspot in neuroscience and new drug development. More than 1,000,000 natural peptides are produced by cone snails, but less than 0.1% of the estimated conotoxins has been characterized to date. Hence, the discovery of novel conotoxins from the huge conotoxin resources with high-throughput and sensitive methods becomes a crucial key for the conotoxin-based drug development. In this review, we introduce the discovery methodology of new conotoxins from various Conus species. It focuses on obtaining full N- to C-terminal sequences, regardless of disulfide bond connectivity through crude venom purification, conotoxin precusor gene cloning, venom duct transcriptomics, venom proteomics and multi-omic methods. The protocols, advantages, disadvantages, and developments of different approaches during the last decade are summarized and the promising prospects are discussed as well.

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