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The two major hallmarks of Alzheimer's disease (AD) are beta-amyloid plaques and neurofibrillary tangles. Amyloid peptide aggregations in the brain cause loss of synaptic connections and subsequent neurotoxicity leading to neurodegeneration and memory deficits. However, the physiological effects of beta-amyloid on early embryonic development still remain unclear. Administration of human beta-amyloid peptide (1-42) through cerebrospinal ventricular injection was carried out at 24 hpf (hours post fertilization) and it was uptaken into the cellular layers of the early ventricular development without any plaque aggregation. Whole-mount Immunostaining of zebrafish embryos injected with the beta-amyloid at 60 hpf revealed the delay in Sox9a expression. Decreased level of cartilage to bone transformation rate in 15 dpf (days post fertilization) zebrafish was observed by differential staining. These results suggest the possible existence of a genetic relationship between extrinsic amyloid peptide and Sox9a expression. Thus, our results demonstrated that the human beta-amyloid influences bone development through Sox9a expression during osteogenesis in zebrafish.

The depletion of dopamine in the striatum region and Lewy bodies are the hallmark characteristics of Parkinson's disease. The pathology also includes the upregulation of various Parkinson's disease (PARK) genes and kinases. Two such kinases, LRRK2 and GSK-3β have been directly implicated in the formation of tau and alpha-synuclein proteins, causing PD. Hesperidin (HES) is a flavanone glycoside that has multiple therapeutic benefits including neuroprotective effects. In this study, we examined the neuroprotective effects of HES against 6-hydroxydopamine (6-OHDA) induced-neurotoxicity in the in-vitro and in-vivo model. Hesperidin significantly protected the SH-SY5Y cells' stress against 6-OHDA induced toxicity by downregulating biomarkers of oxidative stress. Furthermore, HES downregulated the kinases lrrk2 and gsk3β along with casp3, casp9, and polg in the zebrafish model. The treatment with HES also improved the locomotor pattern of zebrafish that was affected by 6-OHDA. This study suggests that hesperidin could be a drug of choice in targeting kinases against a 6-OHDA model of PD.