In summary, we propose that in the AD brain, intraneuronal accumulation of Ab increases the vulnerability of neurons to subsequent chronic exposure to soluble Ab. This combined exposure to intra- and extracellular Ab leads to degenerative changes in neurons and apoptosis through a K + efflux mediated mechanism. Glioblastoma is a highly aggressive brain cancer that has been designated as grade IV, according to the World Health Organization. It represents an extremely invasive form of glioma and has the worst prognosis of any central nervous system disease. Despite aggressive therapies that include combinations of surgery, radiotherapy and chemotherapy, the median postdiagnostic survival period is approximately one year. Many aspects of glioblastoma contribute to its poor prognosis, including the invasive nature of these abnormal cells and the extreme heterogeneity of this cancer. The lack of specificity for the current treatments and their side effects imply the need to develop new therapeutic strategies that target tumor cells. Microtubule-targeting agents represent an important class of drugs used in the treatment of cancers. Microtubules are ubiquitous cellular polymers composed of heterodimers of a- and b-tubulin subunits. They play major roles in several cellular functions, including intracellular TD52 transport, maintenance of cell architecture, cell signaling and mitosis. MTAs exert their antitumoral activity by altering microtubule polymerization and dynamics, which causes growth arrest in mitosis and subsequent cell death by apoptosis. Proteins that compose the intermediate filaments are able to bind free unpolymerized tubulin onto specific sites named tubulin-binding sites and thus can affect microtubule polymerization in vitro and in vivo. A peptide derived from the light neurofilament subunit that corresponds to the sequence of TBS can enter specifically into glioblastoma cells by endocytosis, where it disrupts the microtubule network and induces cell death by apoptosis. Recent studies have confirmed that interactions between intermediate filaments, notably NFL or Vimentin, and key molecules responsible for the plasticity of the mitochondrial network, including Mitofusin-1 and -2 or Dynamin, are necessary to maintain organelle integrity and to allow mitochondrial motility. The fission process ensures mitochondrial structural quality by removing damaged mitochondria through mitophagy and facilitating apoptosis in conditions of cellular stress. The fusion process could be divided into transient and complete fusion. Contrary to complete fusion, the transient process is essential for promoting mitochondrial metabolism and motility by interplaying with the cytoskeletal anchorage. A close relationship has been demonstrated between the oxidative phosphorylation process and mitochondrial network organization, which is controlled by the balance between fusion and fission events. The failure of mitochondrial fusion- fission dynamics has been involved in the pathogenesis of several neurodegenerative diseases and cancers. Mitochondrial biogenesis is dependant of transcription factors such as nuclear respiratory factors and estrogen-related receptors that coordinate the synthesis of OXPHOS complex subunits encoded by the nuclear and mitochondrial genomes. The transcriptional efficiency of these factors is controlled by coactivators from the peroxisome proliferator-activated receptor c coactivator-1 family, i.e., PGC-1a, PGC-1b and the PGC-1-related coactivator, that integrates mitochondrial biogenesis and function to various environmental signals. We previously showed that the ubiquitous PRC member was able to control mitochondrial fission by modulating the Fission-1 expression level in cancer cells, in addition to its effect on mitochondrial biogenesis. Numerous studies have highlighted selected miRNAs related to glioma pathogenesis. Some of them have potential applications as novel diagnostic and prognostic indicators. Thus, the reexpression of miR-34a encoded at Chr1p36.22, a region deleted in many glioblastomas, could be associated with reduced tumor proliferation, cell migration and invasion. Conversely, miR- 21 has been identified as an anti-apoptotic factor and presents a significant up-regulation in glioblastoma, while its inhibition induced apoptosis in glioblastoma cells in vitro and in vivo. This miRNA is involved in the down regulation of the tumor suppressor gene PTEN, in caspase 3/7 activation and confers a drug resistance to cancer cells. Moreover, an over-expression of miR-221 has been linked with increased cellular proliferation and an over-expression of the c-KIT gene. These miRNAs have also recently been related to a pool of miRNAs called mitomiRs, which are associated with the mitochondrial compartment. Their role in the control of mitochondrial functions and cell redox status is now established. In this study, we focused on the role for MTAs in the OXPHOS process and the dynamics of mitochondrial networks. For this purpose, we used the T98G cellular model of human glioblastoma, in which we have previously demonstrated the incorporation and cytoskeleton effect for 10 mM NFL-TBS.40-63 peptide. Previously, we have shown that T98G human glioblastoma cells internalized the NFL-TBS.40-63 peptide at a 10 mM concentration, which induces the disruption of their microtubule network. Consequently, tubulin is aggregated around the nucleus, while cells lose their extensions and become spherical. Using markers of both mitochondrial and microtubule networks, in association with a marked peptide, confocal microscopy showed that the peptide entered in T98G and accumulated in a polarized manner. This was related with a reduction in microtubule and mitochondrial density where the peptide accumulated. It was also convincing for dividing cells where the basis of the midbody was enriched with peptide and mitochondria but completely devoid of microtubule. The NFL-TBS.40-63 peptide was also able to surround microtubule tips and should limit filipodia formation, in accordance with our previous results showing the reduction of cell motility at a low peptide concentration. We observed that the peptide was able to co-localize with both the microtubules and the mitochondria to modify the architecture of their networks contrary to that observed in untreated cells. We also observed that mitochondria could be structured independently of the microtubule network with co-localized mitochondrial network and long chains of NFLTBS. 40-63 peptide sequences.