Evaluation of betulinic acid effects on pain, memory, anxiety, catalepsy, and oxidative stress in animal model of Parkinson's disease.

Parkinson's disease (PD) is known for motor impairments. Betulinic acid (BA) is a natural compound with antioxidant activity. The present study addresses the question of whether BA affects motor and non-motor dysfunctions and molecular changes in the rat model of PD. The right medial forebrain bundle was lesioned by injection of 6-hydroxydopamine in Male Wistar rats (10-12 weeks old, 270-320 g). Animals were divided into Sham, PD, 3 treated groups with BA (0.5, 5, and 10 mg/kg, IP), and a positive control group received L-dopa (20 mg/kg, P.O) for 7 days. rigidity, anxiety, analgesia, and memory were assessed by bar test, open-field, elevated plus-maze (EPM), tail-flick, and shuttle box. Additionally, the malondialdehyde (MDA), Superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, Brain-derived neurotrophic factor (BDNF) and Interleukin 10 (IL10) levels in the whole brain were measured. BA significantly reversed the 6-hydroxydopamine-induced motor and memory complication in the bar test and shuttle box. It modified anxiety-like behavior neither in open-field nor in EPM. It only decreased the time spent in open arms. Moreover, no significant changes were found in the tail-flick between treatment and sham groups. On the other hand, the level of MDA & IL10 were decreased, while the activity of GPx levels of SOD & BDNF in the rats' brains was increased. Our results showed that BA as a free radical scavenger can account for a possible promise as a good therapeutic agent for motor and non-motor complications in PD however further studies may be needed.

MALAT1 lncRNA and Parkinson's Disease: The role in the Pathophysiology and Significance for Diagnostic and Therapeutic Approaches.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder. PD is characterized by progressive loss of dopamine-producing neurons in the substantia nigra (SN) region of brain tissue followed by the α-synuclein-based Lewy bodies' formation. These conditions are manifested by various motor and non-motor symptoms such as resting tremor, limb rigidity, bradykinesia and posture instability, cognitive impairment, sleep disorders, and emotional and memory dysfunctions. Long non-coding RNAs (lncRNAs) are closely related to protein-coding genes and are involved in various biological processes. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) lncRNA is involved in different pathways, including alternative splicing, transcriptional regulation, and post-transcriptional regulation, and also interacts with RNAs as a miRNA sponge. MALAT1 is highly expressed in brain tissues and several lines of evidence suggested it is probably involved in synapse generation and other neurophysiological pathways. This narrative review discussed all aspects of MALAT1-associated mechanisms involved in the PD pathogenesis, i.e., perturbed α-synuclein homeostasis, apoptosis and autophagy, and neuro-inflammation. Lastly, the possible applications of MALAT1 as a diagnostic biomarker and its importance to developing therapeutic strategies were highlighted. The literature search was conducted using neurodegeneration, neurodegenerative disorders, Parkinson's disease, lncRNA, and MALAT1 as search items in Google Scholar, Web of Knowledge, PubMed, and Scopus up to December 2021.