Novel Pharmaceutical Approaches in Dementia

Tanaka, Masaru; Török, Nóra; Vécsei, László

doi:10.1007/978-3-319-56015-1_444-1

Cited by 29 publications

(34 citation statements)

References 69 publications

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“…By 2025, the worldwide prevalence of AD will increase to 100 million or more, leading to a significant financial burden and augmenting the need of a high level of care. Clinical symptoms of AD include cognitive decline, short-term memory failure, orientation problems, and motor abnormalities [ 2 , 3 ]. These deficits are attributed to widespread neuronal loss, glial dysfunction, synaptic degeneration and brain atrophy, and gradual propagation of hallmarks of AD, including amyloid plaques and neurofibrillary tangles (NFTs), throughout the brain [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Alzheimer’s Disease Pathology and Improve Cognitive Deficits

Chen

et al. 2021

Biomedicines

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The accumulation of extracellular β-amyloid (Aβ) plaques within the brain is unique to Alzheimer’s disease (AD) and thought to induce synaptic deficits and neuronal loss. Optimal therapies should tackle the core AD pathophysiology and prevent the decline in memory and cognitive functions. This study aimed to evaluate the therapeutic performance of mesenchymal stem cell-derived exosomes (MSC-exosomes), which are secreted membranous elements encapsulating a variety of MSC factors, on AD. A human neural cell culture model with familial AD (FAD) mutations was established and co-cultured with purified MSC-exosomes. 2-[18F]Fluoro-2-deoxy-d-glucose ([18F]FDG) and novel object recognition (NOR) testing were performed before/after treatment to evaluate the therapeutic effect in vivo. The AD-related pathology and the expression of neuronal memory/synaptic plasticity-related genes were also evaluated. The results showed that MSC-exosomes reduced Aβ expression and restored the expression of neuronal memory/synaptic plasticity-related genes in the cell model. [18F]FDG-PET imaging and cognitive assessment revealed a significant improvement in brain glucose metabolism and cognitive function in AD transgenic mice. The phase of neurons and astrocytes in the brain of AD mice were also found to be regulated after treatment with MSC-exosomes. Our study demonstrates the therapeutic mechanism of MSC-exosomes and provides an alternative therapeutic strategy based on cell-free MSC-exosomes for the treatment of AD.

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Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Alzheimer’s Disease Pathology and Improve Cognitive Deficits

Chen

et al. 2021

Biomedicines

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“…Genome-wide association study has made it feasible to identify associated genes, post-transcriptional modification, single nucleotide polymorphisms, and structural variants as potential biomarkers in multifactorial diseases. Finally, possible interventions through enzymes and metabolites in the kynurenine pathway of tryptophan metabolism in dementia are being currently studied (7). Some of these collaborative efforts are aimed at overcoming the challenge of reliably identifying patients with preclinical AD.…”

Section: Alzheimer's Dementiamentioning

confidence: 99%

Dementia – care until cure: an update on management

Wickramasinghe

Perera

2021

Sri Lanka J. Psyc.

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“…Disturbance of KYN metabolites has been linked to immune disorders, cancers, neurodegenerative diseases, and psychiatric disorders [27]. Furthermore, TRP-KYN metabolites are under extensive research in search of peripheral biomarkers as well as novel drug prototypes for a wide range of diseases [28][29][30][31][32][33][34]. Inflammation activates the TRP-KYN pathway, elevating the levels of oxidative compounds or neurotoxic ligands to receptors of the excitatory glutamatergic nervous system, which damage the peripheral nervous system or CNS through the broken blood-nerve or blood-brain-barrier, respectively [16].…”

Section: Noxious Stimulimentioning

confidence: 99%

Co-Players in Chronic Pain: Neuroinflammation and the Tryptophan-Kynurenine Metabolic Pathway

Tanaka¹,

Török²,

Tóth³

et al. 2021

Preprint

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Chronic pain is an unpleasant sensory and emotional experience that persists or recurs more than three months and may extend beyond the expected time of healing. Recently nociplastic pain has been introduced as a descriptor of mechanism of pain, which is due to disturbance of neural processing without actual or potential tissue damage, appearing to replace a concept of psychogenic pain. An interdisciplinary task force of the International Association for the Study of Pain (IASP) compiled a systematic classification of clinical conditions associated with chronic pain, which was published in 2018 and will officially come into effect in 2022 in the 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11) by the World Health Organization. ICD-11 offers the option for recording the presence of psychological or social factors in chronic pain; however, cognitive, emotional, and social dimensions in the pathogenesis of chronic pain are missing. Earlier pain disorder was defined as a condition with chronic pain associated with psychological factors, but it was replaced with somatic symptom disorder with predominant pain in Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in 2013. Recently clinical nosology is trending toward highlighting neurological pathology of chronic pain, discounting psychological or social factors in the pathogenesis of pain. This review article discusses components of the pain pathway, the component-based mechanisms of pain, central and peripheral sensitization, roles of chronic inflammation, and the involvement of tryptophan-kynurenine pathway metabolites, exploring participations of psychosocial and behavioral factors in central sensitization of diseases progressing into development of chronic pain, comorbid diseases that commonly present a symptom of chronic pain, and psychiatric disorders that manifest chronic pain without obvious actual or potential tissue damage.

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Novel Pharmaceutical Approaches in Dementia

Cited by 29 publications

References 69 publications

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Alzheimer’s Disease Pathology and Improve Cognitive Deficits

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Alzheimer’s Disease Pathology and Improve Cognitive Deficits

Dementia – care until cure: an update on management

Co-Players in Chronic Pain: Neuroinflammation and the Tryptophan-Kynurenine Metabolic Pathway

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