The second most prevalent neurodegenerative disorder in the elderly is Parkinson’s disease (PD). Its etiology is unclear and there are no available disease-modifying medicines. Therefore, more evidence is required concerning its pathogenesis. The use of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the basis of most animal models of PD. MPTP is metabolized by monoamine oxidase B (MAO B) to MPP + and induces the loss of dopaminergic neurons in the substantia nigra in mammals. Zebrafish have been commonly used in developmental biology as a model organism, but owing to its perfect mix of properties, it is now emerging as a model for human diseases. Zebrafish (Danio rerio) are cheap and easy to sustain, evolve rapidly, breed transparent embryos in large amounts, and are readily manipulated by different methods, particularly genetic ones. Furthermore, zebrafish are vertebrate species and mammalian findings obtained from zebrafish may be more applicable than those derived from genetic models of invertebrates such as Drosophila melanogaster and Caenorhabditis elegans. The resemblance cannot be taken for granted, however. The goal of the present review article is to highlight the promise of zebrafish as a PD animal model. As its aminergic structures, MPTP mode of action, and PINK1 roles mimic those of mammalians, zebrafish seems to be a viable model for studying PD. The roles of zebrafish MAO, however, vary from those of the two types of MAO present in mammals. The benefits unique to zebrafish, such as the ability to perform large-scale genetic or drug screens, should be exploited in future experiments utilizing zebrafish PD models.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. It affects the locomotor system, leading to a final severe disability through degeneration of dopaminergic neurons. Despite several therapeutic approaches used, no treatment has been proven to be effective; however, cell therapy may be a promising therapeutic method. In addition, the use of the intranasal (IN) route has been advocated for delivering various therapies to the brain. In the present study, the IN route was used for administration of mesenchymal stem cells (MSCs) in a mouse model of PD, with the aim to evaluate IN delivery as an alternative route for cell based therapy administration in PD. The PD model was developed in C57BL/6 mice using intraperitoneal rotenone administration for 60 consecutive days. MSCs were isolated from the mononuclear cell fraction of pooled bone marrow from C57BL/6 mice and incubated with micrometer-sized iron oxide (MPIO) particles. For IN administration, we used a 20 µl of 5×105 cell suspension. Neurobehavioral assessment of the mice was performed, and after sacrifice, brain sections were stained with Prussian blue to detect the MPIO-labeled MSCs. In addition, immunohistochemical evaluation was conducted to detect tyrosine hydroxylase (TH) antibodies in the corpus striatum and dopaminergic neurons in the substantia nigra pars compacta (SNpc). The neurobehavioral assessment revealed progressive deterioration in the locomotor functions of the rotenone group, which was improved following MSC administration. Histopathological evaluation of brain sections in the rotenone+MSC group revealed successful delivery of MSCs, evidenced by positive Prussian blue staining. Furthermore, rotenone treatment led to significant decrease in dopaminergic neuron number in SNpc, as well as similar decrease in the corpus striatum fiber density. By contrast, in animals receiving IN administration of MSCs, the degeneration caused by rotenone treatment was significantly counteracted. In conclusion, the present study validated that IN delivery of MSCs may be a potential safe, easy and cheap alternative route for stem cell treatment in neurodegenerative disorders.

Alzheimer’s disease (AD) is recognized as a major health hazard that mostly affects people older than 60 years. AD is one of the biggest medical, economic, and social concerns to patients and their caregivers. AD was ranked as the 5^th leading cause of global deaths in 2016 by the World Health Organization (WHO). Many drugs targeting the production, aggregation, and clearance of Aβ plaques failed to give any conclusive clinical outcomes. This mainly stems from the fact that AD is not a disease attributed to a single-gene mutation. Two hallmarks of AD, Aβ plaques and neurofibrillary tangles (NFTs), can simultaneously induce other AD etiologies where every pathway is a loop of consequential events. Therefore, the focus of recent AD research has shifted to exploring other etiologies, such as neuroinflammation and central hyperexcitability. Neuroinflammation results from the hyperactivation of microglia and astrocytes that release pro-inflammatory cytokines due to the neurological insults caused by Aβ plaques and NFTs, eventually leading to synaptic dysfunction and neuronal death. This review will report the failures and side effects of many anti-Aβ drugs. In addition, emerging treatments targeting neuroinflammation in AD, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and receptor-interacting serine/threonine protein kinase 1 (RIPK1), that restore calcium dyshomeostasis and microglia physiological function in clearing Aβ plaques, respectively, will be deliberately discussed. Other novel pharmacotherapy strategies in treating AD, including disease-modifying agents (DMTs), repurposing of medications used to treat non-AD illnesses, and multi target-directed ligands (MTDLs) are also reviewed. These approaches open new doors to the development of AD therapy, especially combination therapy that can cater for several targets simultaneously, hence effectively slowing or stopping AD.

Glia, which was formerly considered to exist just to connect neurons, now plays a key function in a wide range of physiological events, including formation of memory, learning, neuroplasticity, synaptic plasticity, energy consumption, and homeostasis of ions. Glial cells regulate the brain's immune responses and confers nutritional and structural aid to neurons, making them an important player in a broad range of neurological disorders. Alzheimer's, ALS, Parkinson's, frontotemporal dementia (FTD), and epilepsy are a few of the neurodegenerative diseases that have been linked to microglia and astroglia cells, in particular. Synapse growth is aided by glial cell activity, and this activity has an effect on neuronal signalling. Each glial malfunction in diverse neurodegenerative diseases is distinct, and we will discuss its significance in the progression of the illness, as well as its potential for future treatment.

Parkinson’s disease (PD) is the most common brain motor disorder, characterized by a substantial loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Motor impairments, such as dyskinesia, bradykinesia, and resting tremors, are the hallmarks of PD. Despite ongoing research, the exact PD pathogenesis remains elusive due to the disease intricacy and difficulty in conducting human studies. Zebrafish (Danio rerio) has emerged as an ideal model for researching PD pathophysiology. Even though 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been used to induce PD in zebrafish, behavioural findings are frequently limited to a single time point (24 hours post-injection). In this sense, we aim to demonstrate the effects of MPTP on zebrafish swimming behaviour at multiple time points. We administered a single dosage of MPTP (200μg/g bw) via intraperitoneal injection (i/p) and assessed the locomotor activity and swimming pattern at 0h, 24h, and 96h post-injection through an open field test. Analysis of the behaviour revealed significant reductions in swimming velocity (cm/s) and distance travelled (cm), concurrent with an increase in freezing maintenance (duration and bouts) in zebrafish injected with MPTP. In addition, the MPTP-injected zebrafish exhibited complex swimming patterns, as measured by the turn angle, meander, and angular velocity, and showed abnormal swimming phenotypes, including freezing, looping, and erratic movement. To conclude, MPTP administration into adult zebrafish induced hypolocomotion and elicited motor incoordination. Plus, the effects of MPTP were observable 24 hours after the injection and still detectable 96 hours later. These findings contribute to the understanding of MPTP effects on adult zebrafish, particularly in terms of swimming behaviours, and may pave the way for a better understanding of the establishment of PD animal models in the future.