Review Article

Neuropathology and Neurochemistry of Nonmotor Symptoms in Parkinson's Disease

Table 1

Convergence of altered metabolic events in the cerebral cortex in Parkinson disease.

Altered cortical innervation
(i) Dopamine (nigrostriatal and mesocortical pathways):  indirect and direct pathways
(ii) Noradrenaline (locus ceruleus)
(iii) Serotonine (raphe nuclei)
(iv) Acetylcholine (nuclei of the basal forebrain)

Synaptic pathology
(i) ↑ Tau phosphorylation in synaptic fractions
(ii) ↑  α-synuclein phosphorylation in synaptic fractions
(iii) Small α-synuclein aggregates at the synapses
Altered α -synuclein and α-synuclein interactions

(i) Oxidation and phosphorylation of α-synuclein
(ii) Abnormal synuclein interactions with
 (a) rab3a: possible altered synaptic traffic
 (b) rab5: possible altered endocytosis
 (c) rab8: possible altered transport
 (d) PLCβ: altered mGluR1 signalling

Altered mitochondria
(i) ↑ Mitochondrial mass
(ii) Complex I of the respiratory chain
(iii) Mitochondrial O2 uptake
(iv) Oxidative damage of subunits of mitochondrial complex I  and DJ1
(v) (altered DJ1, PINK1, LRRK2, and Htr2 in familial PD)

Increased oxidative damage
(i) ↑ Lipoxidative and glycoxidative damage of proteins and  oxidative damage of DNA
(ii) ↑ Oxidative damage of proteins linked with glycolysis and  energy metabolism
(iii) ↑ Oxidative damage of superoxide dismutase 2
(iv) ↑ Oxidative damage of β-synuclein, α-synuclein, cytoskeletal  proteins and UCHL1

Altered composition of membrane lipids in the grey matter
(i) Total homogenates
(ii) Lipid rafts: ↑ viscosity

Late, secondary events
(i) Synaptic loss
(ii) Lewy bodies and neurites
(iii) Neuronal death