c-Jun N-Terminal Kinases in Alzheimer’s Disease: A Possible Target for the Modulation of the Earliest Alterations

Issue title: Translational Research and Drug Discovery for Neurodegeneration: Challenges for Latin America

Guest editors: K.S. Jagannatha Rao, Gabrielle B. Britton, Luisa Lilia Rocha Arrieta, Norberto Garcia-Cairasco, Alberto Lazarowski, Adrián Palacios, Antoni Camins Espuny and Ricardo B. Maccioni

Article type: Review Article

Authors: Busquets, Oriol^{a; b; c; d; e; 1} | Parcerisas, Antoni^{c; d; f; 1} | Verdaguer, Ester^{c; d; f} | Ettcheto, Miren^{a; c; d} | Camins, Antoni^{a; c; d} | Beas-Zarate, Carlos^g | Castro-Torres, Rubén Darío^{h; *} | Auladell, Carme^{c; d; f; *}

Affiliations: [a] Department of Pharmacology, Toxicology and Therapeutic Chemistry; Pharmacy and Food Sciences Faculty, Universitat de Barcelona, Barcelona, Spain | [b] Department of Biochemistry and Biotechnology, Medicine and Health Sciences Faculty, Universitat Rovira i Virgili, Reus, Spain | [c] Centre for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain | [d] Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain | [e] Dominick P. Purpura Department of Neurosciences, Albert Einstein College of Medicine, New York City, NY, USA | [f] Department of Cell Biology, Physiology and Immunology, Biology Faculty, Universitat de Barcelona, Barcelona, Spain | [g] Department of Cell and Molecular Biology, Laboratory of Neural Regeneration, C.U.C.B.A., Universidad de Guadalajara, Jalisco, Mexico | [h] Department of Cell and Molecular Biology, Laboratory of Biology of Neurotransmission, C.U.C.B.A., Universidad de Guadalajara, Jalisco, Mexico

Correspondence: [*] Correspondence to: Carme Auladell, Centre for Biomedical Research of Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, 28031, Spain. E-mail: [email protected].; Rubén Darío Castro-Torres, Department of Cell and Molecular Biology, Laboratory of Neural Regeneration, C.U.C.B.A., Universidad de Guadalajara, 45200 Jalisco, Mexico. E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Given the highly multifactorial origin of Alzheimer’s disease (AD) neuropathology, disentangling and orderly knowing mechanisms involved in sporadic onset are arduous. Nevertheless, when the elements involved are dissected into smaller pieces, the task becomes more accessible. This review aimed to describe the link between c-Jun N-terminal Kinases (JNKs), master regulators of many cellular functions, and the early alterations of AD: synaptic loss and dysregulation of neuronal transport. Both processes have a role in the posterior cognitive decline observed in AD. The manuscript focuses on the molecular mechanisms of glutamatergic, GABA, and cholinergic synapses altered by the presence of amyloid-β aggregates and hyperphosphorylated tau, as well as on several consequences of the disruption of cellular processes linked to neuronal transport that is controlled by the JNK-JIP (c-jun NH2-terminal kinase (JNK)–interacting proteins (JIPs) complex, including the transport of AβPP or autophagosomes.

Keywords: Alzheimer’s disease, amyloid-β, axonal transport, hyperphosphorylated tau, JNK, synapse loss

DOI: 10.3233/JAD-201053

Journal: Journal of Alzheimer's Disease, vol. 82, no. s1, pp. S127-S139, 2021