scholarly journals d-amino Acids in Health and Disease: A Focus on Cancer

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2205 ◽  
Author(s):  
Jacco J.A.J. Bastings ◽  
Hans M. van Eijk ◽  
Steven W. Olde Damink ◽  
Sander S. Rensen
Keyword(s):  
Amino Acids ◽  
Human Physiology ◽  
Amyotrophic Lateral Sclerosis ◽  
Human Body ◽  
Physiological Processes ◽  
Gut Barrier Function ◽  
Age Related ◽  
Health And Disease ◽  
Living Organisms ◽  
Lateral Sclerosis

d-amino acids, the enantiomeric counterparts of l-amino acids, were long considered to be non-functional or not even present in living organisms. Nowadays, d-amino acids are acknowledged to play important roles in numerous physiological processes in the human body. The most commonly studied link between d-amino acids and human physiology concerns the contribution of d-serine and d-aspartate to neurotransmission. These d-amino acids and several others have also been implicated in regulating innate immunity and gut barrier function. Importantly, the presence of certain d-amino acids in the human body has been linked to several diseases including schizophrenia, amyotrophic lateral sclerosis, and age-related disorders such as cataract and atherosclerosis. Furthermore, increasing evidence supports a role for d-amino acids in the development, pathophysiology, and treatment of cancer. In this review, we aim to provide an overview of the various sources of d-amino acids, their metabolism, as well as their contribution to physiological processes and diseases in man, with a focus on cancer.

scholarly journals The Link between VAPB Loss of Function and Amyotrophic Lateral Sclerosis

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1865
Author(s):  
Nica Borgese ◽  
Nicola Iacomino ◽  
Sara Francesca Colombo ◽  
Francesca Navone
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Adaptor Proteins ◽  
Loss Of Function ◽  
Membrane Contact Sites ◽  
Physiological Processes ◽  
Main Driver ◽  
Single Allele ◽  
Induced Pluripotent ◽  
Lateral Sclerosis

The VAP proteins are integral adaptor proteins of the endoplasmic reticulum (ER) membrane that recruit a myriad of interacting partners to the ER surface. Through these interactions, the VAPs mediate a large number of processes, notably the generation of membrane contact sites between the ER and essentially all other cellular membranes. In 2004, it was discovered that a mutation (p.P56S) in the VAPB paralogue causes a rare form of dominantly inherited familial amyotrophic lateral sclerosis (ALS8). The mutant protein is aggregation-prone, non-functional and unstable, and its expression from a single allele appears to be insufficient to support toxic gain-of-function effects within motor neurons. Instead, loss-of-function of the single wild-type allele is required for pathological effects, and VAPB haploinsufficiency may be the main driver of the disease. In this article, we review the studies on the effects of VAPB deficit in cellular and animal models. Several basic cell physiological processes are affected by downregulation or complete depletion of VAPB, impinging on phosphoinositide homeostasis, Ca2+ signalling, ion transport, neurite extension, and ER stress. In the future, the distinction between the roles of the two VAP paralogues (A and B), as well as studies on motor neurons generated from induced pluripotent stem cells (iPSC) of ALS8 patients will further elucidate the pathogenic basis of p.P56S familial ALS, as well as of other more common forms of the disease.

scholarly journals A modular tool to query and inducibly disrupt biomolecular condensates

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen N. Hernández-Candia ◽  
Sarah Pearce ◽  
Chandra L. Tucker
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cellular Function ◽  
Biological Role ◽  
Cellular Biology ◽  
Condensate Formation ◽  
Health And Disease ◽  
Lateral Sclerosis

AbstractDynamic membraneless compartments formed by protein condensates have multifunctional roles in cellular biology. Tools that inducibly trigger condensate formation have been useful for exploring their cellular function, however, there are few tools that provide inducible control over condensate disruption. To address this need we developed DisCo (Disassembly of Condensates), which relies on the use of chemical dimerizers to inducibly recruit a ligand to the condensate-forming protein, triggering condensate dissociation. We demonstrate use of DisCo to disrupt condensates of FUS, associated with amyotrophic lateral sclerosis, and to prevent formation of polyglutamine-containing huntingtin condensates, associated with Huntington’s disease. In addition, we combined DisCo with a tool to induce condensates with light, CRY2olig, achieving bidirectional control of condensate formation and disassembly using orthogonal inputs of light and rapamycin. Our results demonstrate a method to manipulate condensate states that will have broad utility, enabling better understanding of the biological role of condensates in health and disease.

scholarly journals The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS)

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sarah L. Boddy ◽  
Ilaria Giovannelli ◽  
Matilde Sassani ◽  
Johnathan Cooper-Knock ◽  
Michael P. Snyder ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Phenotypic Variability ◽  
Personalised Medicine ◽  
Main Body ◽  
Body Of Knowledge ◽  
Environmental Component ◽  
Health And Disease ◽  
Lateral Sclerosis

Abstract Background Much progress has been made in mapping genetic abnormalities linked to amyotrophic lateral sclerosis (ALS), but the majority of cases still present with no known underlying cause. Furthermore, even in families with a shared genetic abnormality there is significant phenotypic variability, suggesting that non-genetic elements may modify pathogenesis. Identification of such disease-modifiers is important as they might represent new therapeutic targets. A growing body of research has begun to shed light on the role played by the gut microbiome in health and disease with a number of studies linking abnormalities to ALS. Main body The microbiome refers to the genes belonging to the myriad different microorganisms that live within and upon us, collectively known as the microbiota. Most of these microbes are found in the intestines, where they play important roles in digestion and the generation of key metabolites including neurotransmitters. The gut microbiota is an important aspect of the environment in which our bodies operate and inter-individual differences may be key to explaining the different disease outcomes seen in ALS. Work has begun to investigate animal models of the disease, and the gut microbiomes of people living with ALS, revealing changes in the microbial communities of these groups. The current body of knowledge will be summarised in this review. Advances in microbiome sequencing methods will be highlighted, as their improved resolution now enables researchers to further explore differences at a functional level. Proposed mechanisms connecting the gut microbiome to neurodegeneration will also be considered, including direct effects via metabolites released into the host circulation and indirect effects on bioavailability of nutrients and even medications. Conclusion Profiling of the gut microbiome has the potential to add an environmental component to rapidly advancing studies of ALS genetics and move research a step further towards personalised medicine for this disease. Moreover, should compelling evidence of upstream neurotoxicity or neuroprotection initiated by gut microbiota emerge, modification of the microbiome will represent a potential new avenue for disease modifying therapies. For an intractable condition with few current therapeutic options, further research into the ALS microbiome is of crucial importance.

Motor unit hyperexcitability in amyotrophic lateral sclerosis vs amino acids acting as neurotransmitters

2002 ◽  
Vol 106 (1) ◽  
pp. 34-38 ◽  
Author(s):  
A. Kostera-Pruszczyk ◽  
I. Niebroj-Dobosz ◽  
B. Emeryk-Szajewska ◽  
A. Karwańska ◽  
K. Rowińska-Marcińska
Keyword(s):  
Amino Acids ◽  
Amyotrophic Lateral Sclerosis ◽  
Motor Unit ◽  
Lateral Sclerosis

scholarly journals Therapeutic Depletion of Axotomy Competent Cells in Amyotrophic Lateral Sclerosis (ALS)

2019 ◽  
Vol 2 (1) ◽  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Protein Networks ◽  
Large Protein ◽  
Anatomical Structures ◽  
Therapy Options ◽  
New Therapy ◽  
Competent Cells ◽  
Health And Disease ◽  
Insight Into ◽  
Lateral Sclerosis

The present paper addresses anatomically resolved protein networks by using the Imaging Cycler Microscopy (ICM/TIS) [1,2]. ICM is capable of resolving protein networks in intact anatomical structures at a power of combinatorial molecular resolution of 65,553k , where k is the number of co-mapped proteins, e.g. 100 proteins [1-4]. This method provides insight into the laws of the spatial communication of large protein networks in health and disease, which is essential for new therapy options in diseases.

Complex behavioral and synaptic effects of dietary branched chain amino acids in a mouse model of amyotrophic lateral sclerosis

2011 ◽  
Vol 55 (4) ◽  
pp. 541-552 ◽  
Author(s):  
Aldina Venerosi ◽  
Alberto Martire ◽  
Angela Rungi ◽  
Massimo Pieri ◽  
Antonella Ferrante ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Branched Chain Amino Acids ◽  
Branched Chain ◽  
Synaptic Effects ◽  
Lateral Sclerosis

scholarly journals D-Serine in Neurobiology: CNS Neurotransmission and Neuromodulation

2014 ◽  
Vol 41 (2) ◽  
pp. 164-176 ◽  
Author(s):  
Sanaa K. Bardaweel ◽  
Muhammed Alzweiri ◽  
Aman A. Ishaqat
Keyword(s):  
Amino Acids ◽  
Central Nervous System ◽  
Human Physiology ◽  
Nervous System ◽  
Living Systems ◽  
Cns Development ◽  
Human Central Nervous System ◽  
High Affinity ◽  
Aspartate Receptor ◽  
Living Organisms

Homochirality is fundamental for life. L-Amino acids are exclusively used as substrates for the polymerization and formation of peptides and proteins in living systems. However, D- amino acids were recently detected in various living organisms, including mammals. Of these D-amino acids, D-serine has been most extensively studied. D-Serine was found to play an important role as a neurotransmitter in the human central nervous system (CNS) by binding to the N-methyl- D-aspartate receptor (NMDAr). D-Serine binds with high affinity to a co-agonist site at the NMDAr and, along with glutamate, mediates several vital physiological and pathological processes, including NMDAr transmission, synaptic plasticity and neurotoxicity. Therefore, a key role for D-serine as a determinant of NMDAr mediated neurotransmission in mammalian CNS has been suggested. In this context, we review the known functions of D-serine in human physiology, such as CNS development, and pathology, such as neuro-psychiatric and neurodegenerative diseases related to NMDAr dysfunction.

Sign in / Sign up

Export Citation Format

Share Document