Cellular Transport Mechanisms in Neurodegenerative Diseases

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Background

Age-related neurodegenerative diseases are complex disorders that, despite their clinical and pathologic diversity, share certain basic processes such as the build-up of misfolded, aberrant proteins. Alzheimer’s disease (AD) is the single greatest cause of dementia in old age. Given the rising life expectancy in industrialized countries, and thus the increasing risk of developing this devastating disease, there is a pressing need for an effective therapeutic approach. However, to date, despite intensive research, there is no truly disease-modifying therapy for AD and most other neurodegenerative diseases such as Parkinson’s disease, prion disorders, frontotemporal dementia or motor neuron diseases. Thus, a fuller understanding of fundamental pathogenic mechanisms that drive neurodegenerative processes is a critical need.

In recent years, research has focussed on different types of transport processes for various molecules that are involved in the accumulation of pathogenic proteins such as beta-amyloid or tau-protein, or that play a role in the dysfunction and loss of brain cells. One major point of interest in this regard is the blood-brain barrier (BBB). There are several types of influx or efflux transporters at the BBB, such as Lipoprotein-transporters, ABC-transporters (eg ABCA, ABCB, ABCG), organic anion transporters, organic cation transporters, organic cation transporter novel type transporters, and monocarboxylic acid transporters. LRP1, RAGE and P-gp play an important role in the homeostasis of brain- and blood-derived beta-amyloid. Metal transporters for copper, zinc, iron or aluminium are responsible for maintaining the required supply of these elements for many enzymes that are important for cellular function and are thought to contribute to metal-induced neurodegeneration. Furthermore, calcium homeostasis is directly related to the cell death/survival equilibrium; thus, regulation of calcium homeostasis by targeting calcium channels could lead to the development of novel neuroprotective agents.

We ask investigators to contribute original research articles, as well as review articles or case reports, that will stimulate the continuing efforts to understand the molecular pathology underlying transport processes in neurodegenerative disorders.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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