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Consequently, optimization of the strategies for more precise targeting of astrocytes, microglia, and neurons is much needed to develop the best possible therapies with the least neurotoxicity ( 7 Recent advances and clinical trials for neurodegenerative diseases 7.1 NP-based siRNA delivery for ADs The instability of siRNA therapy in the circulation and the fact that it is unable to reach target cells in the central nervous system ( Nanoparticles delivery systems have now emerged as a powerful strategy for facilitating the passage of siRNA over the blood–brain barrier for AD therapy ( Targeting the APOE ε4 allele or inhibiting TREM2 in microglia, leads to clearance of Aβ, decreasing the inflammation of the nervous system, and slowing AD progression ( The delivery of siRNA by nanoparticles has been examined on genes associated with immune response, lipid metabolism and genes coding receptors expressed on myeloid cells 2 (TREM2) and apolipoprotein E (APOE) ( Molecular structures of siRNA are subjected to chemical modifications, such as the addition of 2′-O-methyl or 2′-fluoro replacements (107, 108)