C-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) provides therapeutic effects in motor impairments associated with Parkinson disease (PD), and provides long lasting antidepressant effects, thus useful in treating and mitigating depression, particularly PD-depression co-morbid condition. A method for treating or mitigating depression, including administrating an effective amount of C-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) to a subject in need thereof. A method for treating or mitigating motor impairments associated with Parkinson's disease (PD), including administrating an effective amount of C-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) to a subject in need thereof.