Neurodegeneration and Cancers

Dear Colleagues,

Neurodegeneration and cancer are among the biggest causes of morbidity and mortality in developed countries. Despite fundamental differences at various levels, these two disease classes share striking commonalities: Both entities are associated with molecular and cellular hallmarks of aging, and mechanisms implicated in aging are crucial in the pathogenesis of both disorders. Among such signatures, genomic stress appears to be of particular relevance as it results in, e.g., DNA strand breaks, gene copy number alterations, and telomere instability. Understudied in the context of DNA integrity are modulators of genomic plasticity, such as extrachromosomal circular DNAs, and their potential to change gene dosages and cellular biology in virtually any cell and tissue type. Similar considerations relate to the class of multitarget microRNAs, which are evidenced to interfere with genes and cellular pathways involved in both carcinogenesis and neuropathologies. Furthermore, microRNAs influence oncogene-induced senescence and might regulate senescence independently of a tumor environment.

Tightly linked to these DNA alterations is the observation that several neurodegenerative pathologies, similar to cancer, are apparently initiated by a loss in cell cycle control. Whereas defective cell cycle surveillance is causative in excessive cell proliferation in cancer, loss in cell cycle repression in the nominally postmitotic neuronal context elicits atypical abortive cell cycle events that will either eliminate a neuron by apoptosis or be putatively repurposed as an alternative DNA repair strategy. Remarkable in this context is the observation that neurons can adopt senescence-like features in terms of marker expression and telomere erosion, similar to the signs of replicative senescence typical for cells with a high proliferative index. Long-term senescence changes the cellular milieu and triggers the senescence-associated secretory phenotype that can drive chronic inflammation and provide a microenvironment favorable for malignant cell transformation, tumor relapse and immune escape, as well as neurodegeneration. The intricate interplay between cancer and neurodegeneration also involves other immunological and inflammatory responses, as evidenced for paraneoplastic syndromes that affect the nervous system and the neurodegenerative features manifest in malignant histiocytosis.

Other well-studied examples of cellular events overlapping in cancer and neurodegeneration include epigenetic alterations, loss of protein and metabolic homeostasis, mitochondrial dysfunction, increased inflammation, disturbed intercellular communication and autophagy, as well as stem cell exhaustion.

In summary, such recent discoveries draw a picture of a broad overlap of the mechanisms that converge at the interface of cancer and neurodegeneration. Accordingly, research in neurodegeneration is expected to profit from breakthrough investigations in cancer and vice versa, and antitumor drug interventions have already been proven to be beneficial in neurodegeneration. Since both pathologies are strongly age-related, future aspects might also focus on mechanisms linked to antagonistic pleiotropy—a functional switch related to aging.

This Special Issue invites contributions based on original research manuscripts, review articles, and perspectives that address the molecular, cellular, and pathophysiological interplay of oncogenesis and neurodegeneration and provide a preview for future experimental designs and therapeutic approaches that consider overlapping beneficial roles, while considering putative ambivalent roles in cancer surveillance or neuroprotection.

Dr. Alexandra Kretz
Dr. Annamaria Brioli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• Aging
• Cancer
• Cancer treatment
• Cell cycle
• DNA damage
• Extrachromosomal circular DNA
• Genomic instability
• Hematological disorders
• Neurodegeneration
• Neurodegeneration treatment
• Senescence