Biological Pathways and Molecular Mechanisms of Dementia—Second Edition

Dear Colleagues,

Dementia is one of the most serious health problems among the elderly, for which only limited medical treatments are available. Molecular pathological studies of dementia disorders, such as Alzheimer’s disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB), have greatly advanced along with the discoveries of the genes associated with their familial forms as well as their risk genes. Although genome-wide association studies have also identified genes which increase the risk, the etiologies of the sporadic forms of these disorders remain elusive. Notably, recent evidence suggests that pathological hallmark proteins, such as amyloid-β (Aβ), tau, TDP-43, FUS, and α-synuclein, are linked to various biological and molecular pathways: enzymes including proteases (e.g., α-, β-, γ-secretases), kinases, phosphatases, acetylcholine esterase, and glucocerebrosidase; neurotransmitters, neurotrophic factors, hormones, and other biological ligands and their receptors; lipids and apolipoproteins and their receptors; cell death pathways, including apoptosis and necroptosis; intracellular transport systems, including axonal transport; proteostasis, including ubiquitin proteasome systems (UPSs), autophagy, and mitophagy; molecules involved in stress responses, including sirtuins; inflammatory molecules, including cytokines and chemokines; transcription factors; microRNAs; and pathways of Aβ clearance from the brain. These biological pathways and factors are generally maintained in a healthy status, but their dysregulation and/or functional perturbation may be critically involved in the pathological mechanisms of dementia disorders. Elucidating the molecular mechanisms underlying the characteristic neuropathological conditions would help to develop new therapeutic approaches.

This Special Issue will present original research articles that investigate the molecular mechanisms of dementia disorders from the above-mentioned aspects, as well as comprehensive review articles that cover such specific topics.

Dr. Wataru Araki
Dr. Madepalli K. Lakshmana
Guest Editors

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