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. 2018 Feb 12;10:12. doi: 10.3389/fnagi.2018.00012

Table 1.

Parkinson's disease: from hallmarks to therapy.

Hallmarks Genetic factors Environmental factors Protective factors Therapy

  • Selective mDA neurodegeneration in the SNpc with concurrent loss of mDA neuronal afferents to striatum and putamen

  • α-SYN aggregation (Lewy bodies and Lewy neurites formation) indicative of ongoing degeneration

  • Astro and microgliosis (astrocyte hypertrophy, M1-microglial morphological and functional shift)

  • PARK Genes (α-SYN/PARK1, LRRK2/PARK8§°, PRKN/PARK2§°, VPS35/PARK17§, UCH-L1/PARK5, GBA§

  • MAPTau§°

  • Dopaminergic related genes (DA-receptors, DA-transporter, TH, COMT, MAO)

  • GSK-3β§°

  • Xenobiotic Metabolism/Detox-related genes (P450IID1, CYP1A1, NAT1, HMOX1§°, GST, NQO2)

  • APOE

  • Neurotrophic genes (NURR1§, NGF, BDNF)

  • Inflammatory related genes (iNOS, TNF-α, IL-1β, IL-6, ER-β)§°

  • Aging§°

  • Rural living herbicides and pesticides exposure (paraquat, rotenone, organochlorines, carbamates)§°, metal exposure°

  • Head injuries

  • Estrogen deficiency (women)§°

  • Infectious diseases during childhood§°

  • Maternal factors/ early-life events (virus, drugs, endotoxins, hormonal deficits)°

  • Drug-induced parkinsonism (drug abuse, neuroleptics, calcium-channel blockers)°

  • miRNAs (miR-155, miR-7116-5p)°

  • Chronic use of NSAIDS (reduces PD risk)§*; **

  • Estrogen replacement therapy (post-menopausal women, OVX animals)*

  • Dietary factors/life style (tea, polyphenols, wine components, curcumin, coffee, tobacco)*

  • Environment (Exercise, social interactions)§**

  • miRNA (miR-7)*

  • Symptomatic: L-DOPA or DAergic agents administration (relieve motor symptoms, do not prevent disease progression)

  • Neuroprotective/symptomatic (selegiline, rasagiline)

  • Cell based therapies (re-introducing DA-producing cells, embryonic, NSCs, treated iPSCs, to replenish DA stores and alleviate/cure PD

  • Combined therapies (anti-oxidants, anti-inflammatories, GSK-3β-inhibitors, protective factors to boost endogenous neurogenesis and mDA neuro-restoration)
§

Wnt/β-CAT dysregulation in the reported conditions.

°

Activation of microglia and pro-inflammatory mediators in animal models of PD under the reported treatments.

*

Mitigation/inhibition of microglial activation in animal models of PD under the reported treatments.

**

Enhanced neurogenesis/synaptic plasticity and glial proliferation.