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Future efforts should focus on developing responsive delivery systems (e.g., oxidative stress-sensitive controlled-release carriers, ultrasound-mediated reversible blood-brain barrier opening) to achieve non-invasive, lesion-specific targeting while minimizing off-target effects

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Carvalho RD, Breyner N, Menezes-Garcia Z, Rodrigues NM, Lemos L, Maioli TU, et al

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Abbreviations AANAT: Arylalkylamine N-acetyltransferase AD: Alzheimers Disease AMPK: AMP-activated Protein Kinase ApEn: Approximate Entropy APP/APPL: Amyloid Precursor Protein/APP-like protein AQP4: Aquaporin-4 ASPS: Advanced Sleep Phase Syndrome ATP: Adenosine Triphosphate AVP: Arginine Vasopressin Bdnf : Brain-Derived Neurotrophic Factor BMAL1 : Brain and Muscle ARNT-Like 1 BP: Blood pressure CALB: Candida antarctica Lipase B cAMP: Cyclic Adenosine Monophosphate CAT: Catalase Cirp : Cold-Inducible RNA-Binding Protein CK1/: Casein Kinase 1 delta/epsilon CLOCK : Circadian Locomotor Output Cycles Kaput CMRO: Cerebral Metabolic Rate of Oxygen Creb1: CAMP Response Element-Binding Protein 1 Cry1/2 : Cryptochrome 1 And 2 CRY1/2: Cryptochrome 1 and 2 proteins CTS: Circadian Timing System dBACE: Drosophila Beta-Site APP Cleaving Enzyme Dbp : D-site Binding Protein Dec : Differentiated Embryo Chondrocyte (DEC family proteins, circadian regulators) DHEA: Dehydroepiandrosterone dLAN: Dim Light at Night DNA: Deoxyribonucleic Acid Drp1: Dynamin-Related Protein 1 DSPS: Delayed Sleep Phase Syndrome Egr-1: Early Growth Response 1 FSH: Follicle Stimulating Hormone GH: Growth Hormone GHRH: Growth Hormone Releasing Hormone GLUT4/1: Glucose Transporter 4/1 GnRH: Gonadotropin-Releasing Hormone GPx: Glutathione Peroxidase GST: Glutathione S-Transferase GTP: Guanosine Triphosphate HDAC3: Histone Deacetylase 3 HPA Axis: HypothalamicPituitaryAdrenal Axis HRV: Heart Rate Variability IGF-1: Insulin-like Growth Factor 1 IL-6: Interleukin-6 ipRGCs: Intrinsically Photosensitive Retinal Ganglion Cells Klf10 : Kruppel-like Factor 10 Klf4 : Kruppel-Like Factor 4 LDH / Ldh: Lactate Dehydrogenase LH: Luteinizing Hormone LLCs: Late-Life Cyclers LPO: Lipid Peroxidation MESOR: Midline Estimating Statistic of Rhythm Mfn2: Mitofusin 2 mRNA: Messenger RNA mTOR: Mechanistic Target of Rapamycin NAD + : Nicotinamide Adenine Dinucleotide (oxidised form) NAMPT/Nampt: Nicotinamide Phosphoribosyltransferase (protein and gene) Nfil3 : Nuclear Factor, Interleukin 3 Regulated NF-B: Nuclear Factor kappa-light-chain-enhancer of activated B cells NO: Nitric Oxide NPY: Neuropeptide Y NREM/REM: Non-Rapid Eye Movement / Rapid Eye Movement (sleep stages) NRF1: Nuclear Respiratory Factor 1 Nrf2 : Nuclear Factor Erythroid 2related Factor 2 OXPHOS: Oxidative Phosphorylation PD: Parkinsons Disease PDGF: Platelet-Derived Growth Factor Per1/2: Per1, Per2 PER1/2: Period 1/2 protein PFC: Prefrontal Cortex PGC-1: Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha PINK1 : PTEN-Induced Putative Kinase 1 PPAR: Peroxisome Proliferator-Activated Receptor Gamma REV-ERB : Reverse-Erb Alpha (Nuclear Receptor Subfamily 1, Group D, Member1 or NR1D1 nuclear receptor) Rev-erb: Reverse-Erb Alpha ROR : Retinoic Acid Receptor-Related Orphan Receptor ROS: Reactive Oxygen Species rSirt1 : Sirtuin 1 SASP: Senescence-Associated Secretory Phenotype SCN: Suprachiasmatic Nucleus SCR: Sleep and Circadian Rhythm SIRT1/3 : Sirtuin 1/3 (NAD-dependent deacetylase) SLOB: Slowpoke Binding Protein SOD: Superoxide Dismutase T3/T4: Triiodothyronine/Thyroxine TERT: Telomerase Reverse Transcriptase TLR4/TLR9 : Toll-Like Receptor 4/9 TNF- : Tumor Necrosis Factor Alpha TRH: Thyrotropin-Releasing Hormone Trkb : Tropomyosin Receptor Kinase B TSH: Thyroid-Stimulating Hormone TTFL: Transcription-Translation Feedback Loop VD: Vascular Dementia VIP: Vasoactive Intestinal Peptide References Acosta-Rodrguez VA, Rijo-Ferreira F, Green CB, Takahashi JS (2021) Importance of circadian timing for aging and longevity

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