Novel Etiological and Therapeutic Strategies for Neurodiseases: RNA Editing Enzyme Abnormality in Sporadic Amyotrophic Lateral Sclerosis

Hideyama, Takuto; Yamashita, Takenari; Nishimoto, Yoshinori; Suzuki, Takeshi; Kwak, Shin

doi:10.1254/jphs.09r21fm

Cited by 10 publications

(6 citation statements)

References 36 publications

(25 reference statements)

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“…1). Improper ADAR functioning has been correlated with several important human diseases [35] such as amyotrophic lateral sclerosis [36][37][38], depression [39][40][41][42][43] and epilepsy [44,45]. In addition, the development of a genetic linkage map of the human pigmentation disease called dyschromatosis symmetrica hereditaria has led to the identification of ADAR1 as the responsible gene [46,47].…”

Section: Introductionmentioning

confidence: 99%

Activity Regulation of Adenosine Deaminases Acting on RNA (ADARs)

2011

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Adenosine deaminases acting on RNA (ADARs) are the enzymes that are responsible for the A to I RNA editing process in mammals, which is an important mechanism that increases molecular diversity. A to I RNA editing consists of an enzymatic conversion of specific adenosine in pre-mRNA, leading to alteration of the properties of both the RNA itself and the translated protein. Currently, the importance of this phenomenon is increasingly recognized as it affects a diverse set of cellular pathways. ADAR function within the cell, especially in the neurons, is to diversify the features of a limited set of unique transcripts, mostly neurotransmitter receptors; however, a growing set of target is going to be discovered, increasing the importance of the RNA editing event in the proper physiology of the cell. Despite the functional relevance of these enzymes, there is a gap of knowledge in the mechanisms that regulate ADAR activity and consequently about the modulation of RNA editing process. This review summarizes ongoing investigations of ADAR regulation at the transcriptional, post-transcriptional and post-translational level and addresses new hypothetical mechanisms that are capable of modulating ADAR activity, including subcellular localization, dimerization and interaction with trans-acting factors.

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Section: Introductionmentioning

confidence: 99%

Activity Regulation of Adenosine Deaminases Acting on RNA (ADARs)

2011

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“…ALS, also known as Lou Gehrig's disease, is a life-threatening ND involved in the upper and lower motor neurons over the spinal cord, brain stem and the related motor cortex [84]. The mean onset age is about 55 years old, and the incidence is around 1-2 per 100,000 per year with 3-5 years of survival after diagnosis [85,86].…”

Section: Amyotrophic Lateral Sclerosis (Als)mentioning

confidence: 99%

Intra-maxillary Molecular Releasing and its Application in the Assistance of Neurodegenerative Disease Therapeutics

J¹

2016

IJCTD

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Neurodegenerative disease (ND) is a complex concept involves multiple pathogenesis including neuronal demyelination, apoptosis under oxidative stress, neuroinflammation with further cortical and spinal atrophy, which may lead to cognition impairment and multiple neural dysfunctions. It may present as a chronic and irreversibly progressive disorder and shows the common pathological pictures among its various types including Alzheimer's disease (AD), Parkinson's disease (AD), Huntington's disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). The symptoms often occur among the elderly above 50 years old and last from years to decades. Such facts lead ND as the highest priority to geriatrics and its related medical care. Due to its chronic progressively characteristics, regularly invasive procedure arrangements may face the difficulty and regarded as unbearable in the clinical practice. Unfortunately, current available therapy is mainly on symptom relief and the potential therapeutic targets may focus on the macromolecules including oligomer, peptides, or even functional proteins with the quaternary structure since multiple proteinopathy involvement in ND pathogenesis. Such macromolecular administrations cause the challenges in the routine drug delivery selections due to the impossibility of the traditional oral intake.Intra-maxillary molecular releasing is a newly drug delivery pathway via dental implant and may directly reach the inside bone marrow. It presents the advantages in long-term and continuous macromolecular releasing with relative painless process, which is appropriate for further applications in ND therapeutics. The stability of dental implant inside the oral cavity has also been proved for decades among more than millions around the world. However, such delivery pathway is currently under development and further interdisciplinary investigations are needed including therapeutics, pharmacokinetics, neurology, molecular biology, clinical dentistry, chemical engineering, automatics and further complementary metal-oxidesemiconductor (CMOS) technology to ensure the efficiency and prove the safety concern.

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“…Specifically, the upper and lower motor neurons die, leading to progressive paralysis [60]. Over 150 years ago, the classic hallmarks of this disease, including the death of motor neurons and progressive atrophy, were described [50].…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Stem cells for the treatment of neurodegenerative diseases

2010

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Stem cells offer an enormous pool of resources for the understanding of the human body. One proposed use of stem cells has been as an autologous therapy. The use of stem cells for neurodegenerative diseases has become of interest. Clinical applications of stem cells for Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis will increase in the coming years, and although great care will need to be taken when moving forward with prospective treatments, the application of stem cells is highly promising.

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Novel Etiological and Therapeutic Strategies for Neurodiseases: RNA Editing Enzyme Abnormality in Sporadic Amyotrophic Lateral Sclerosis

Cited by 10 publications

References 36 publications

Activity Regulation of Adenosine Deaminases Acting on RNA (ADARs)

Activity Regulation of Adenosine Deaminases Acting on RNA (ADARs)

Intra-maxillary Molecular Releasing and its Application in the Assistance of Neurodegenerative Disease Therapeutics

Stem cells for the treatment of neurodegenerative diseases

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