Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by the loss of dopamine-producing neurons in the substantia nigra, leading to motor symptoms such as bradykinesia, rigidity, and tremor, as well as non-motor symptoms including cognitive and mood-related changes. Since diagnosis often occurs after substantial neuronal loss, understanding the mechanisms underlying disease progression and identifying early pathological changes remain important challenges. Longitudinal clinical studies have improved our understanding of the prodromal phase of PD, while therapeutic approaches needs deeper delve in to pathology of neural circuitry system such as nigrostriatal pathway at prodromal phase. Our laboratory with the purpose to investigate such cellular and molecular mechanisms in PD progression uses mice and cellular models. In our MPTP-based model, we examine the time-dependent degeneration of dopaminergic neurons and the emergence of motor and non-motor behavioural changes. Behavioural findings are integrated with molecular, biochemical, and histological analyses to assess neuronal integrity and synaptic alterations in the substantia nigra and striatum. Using A53T α-synuclein transgenic mice, we investigate disease progression from early pathological changes to motor dysfunction, with a particular focus on alterations in autophagy and mitophagy and their relationship with α-synuclein pathology, synaptic dysfunction, and dopaminergic neuronal loss. We also use α-synuclein pre-formed fibrils (PFFs) to study the initiation, propagation, and amplification of α-synuclein pathology. Together, these complementary approaches enable us to investigate dopaminergic neurodegeneration, α-synuclein pathology, synaptic dysfunction, and disease progression in PD.