Neurological Sciences

, Volume 40, Issue 1, pp 13–23 | Cite as

Understanding multifactorial architecture of Parkinson’s disease: pathophysiology to management

  • Ramandeep Kaur
  • Sidharth Mehan
  • Shamsher Singh
Review Article


Parkinson’s disease (PD) is the second most common multifactorial neurodegenerative disorder affecting 3% of population during elder age. The loss of substantia nigra, pars compacta (SNpc) neurons and deficiency of striatal dopaminergic neurons produces stables motor deficient. Further, increase alpha-synuclein accumulation, mitochondrial dysfunction, oxidative stress, excitotoxicity, and neuroinflammation plays a crucial role in the pathogenesis of PD. Alpha-synuclein protein encodes for SNCA gene and disturbs the normal physiological neuronal signaling via altering mitochondrial homeostasis. The level of α-synuclein is increased in both normal aging and PD brain to a greater extent and secondly reduced clearance results in accumulation of Lewy bodies (LB). Emerging evidences indicate that mitochondrial dysfunction might be a common cause but pathological insult through protein misfolding, aggregation, and accumulation leads to neuronal apoptosis. The observation supporting that expression of DJ-1, LLRK2, PARKIN, PINK1, and excessive excitotoxicity mediated by dysbalance between GABA and glutamate reduced mitochondrial functioning and increased neurotoxicity. Therefore, the present review summarizes the various pathological mechanisms and also explores the therapeutic strategies which could be useful to ameliorate movement disorder like Parkinsonism.


Parkinson disease Substantia nigra pars compacta Dopaminergic neurons Neurotransmitters 



The authors are highly thankful to Dr. Shamsher Singh, Associate professor, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India for providing support and keen guidance.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Neuroscience Division, Department of PharmacologyIndo-Soviet Friendship College of PharmacyMogaIndia

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