Erythrocyte membrane in the evaluation of neurodegenerative disorders

Abstract

Neurodegenerative diseases have many similar pathological conditions, and very few studies exist which detail their molecular features. Proteins like Na⁺/K⁺-ATPase (NKA), α-spectrin (SPTA) and drebrin have been reported to be involved in the integrity of neuronal cell membrane and their functions. Furthermore, recent studies have highlighted their implication in neurodegeneration. In the current study, we wanted to identify the role of NKA, SPTA and drebrin in the erythrocyte membranes obtained from the blood of patients with neurodegenerative disorders (NDs) subjected to motor impairment such as Parkinson's disease, amyotrophic lateral sclerosis, ataxia and dementia. We have studied the activity of NKA and the expression of NKA, SPTA and drebrin in the erythrocyte membrane by quantitative real-time PCR and Western blot obtained from the blood samples of patients with NDs culminating in movement and memory dysfunction. We observed a significant reduction in the expressions of NKA, SPTA and drebrin when compared to control and significant variations among the recruited ND samples. On correlating, we found a significant relationship between the expressions and the clinical features such as bradykinesia. Thus, we suggest that the reduction in the expressions of NKA, SPTA and drebrin could function as tools of assessment and speculate the particular neurodegenerative condition.

Keywords: K+-ATPase; Na+; drebrin; neurodegeneration and movement disorder; spectrin.

Figure 1

(A) The representative histogram of the activity of NKA activity of control and the recruited neurodegenerative subjects. ANOVA was performed (p≤0.05) compared with (a) control, (b) Parkinson’s disease, (c) amyotrophic lateral sclerosis, (d) ataxia and (e) dementia. Error bars indicate SEM; (B) data on the linear correlation analysis between MBRS and Parkinson’s disease; (C) data on the linear correlation analysis between MBRS and amyotrophic lateral sclerosis; (D) data on the linear correlation analysis between MBRS and ataxia. Nonparametric correlation (Spearman’s rho, r) was used to correlate clinical features (movement dysfunction in accordance with MBRS and age) and NKA activity in ND subjects with movement disorders; *p≤0.05 indicates significance; **p≤0.01 indicates highly significant. Abbreviations: ANOVA, analysis of variance; PD, Parkinson’s disease; ALS, amyotrophic lateral sclerosis; DM, dementia; SEM, standard error of the mean; MBRS, Modified Bradykinesia Rating Scale; NKA, Na⁺/K⁺-ATPase; ND, neurogenerative disorder.

Figure 2

(A) Representative Western blot results (experiments were performed in triplicate); (B) relative density graphs of mean ± SD. ANOVA was performed (p≤0.05) compared with (a) control, (a) Parkinson’s disease, (a) amyotrophic lateral sclerosis, (a) ataxia, (a) dementia. Error bars indicate SEM. *p≤0.05 indicates significance; **p≤0.01 indicates highly significant. Abbreviations: ANOVA, analysis of variance; SEM, standard error of the mean; PD, Parkinson’s disease; ALS, amyotrophic lateral sclerosis; DM, dementia.

Figure 3

Data on qRT PCR analysis between control and neurodegenerative subjects: (A) NKAα₂, (B) NKAα₃, (C) SPTA and (D) drebrin. ANOVA was performed using the mean fold change (p≤0.05) compared with (a) control, (b) Parkinson’s disease, (c) amyotrophic lateral sclerosis, (d) ataxia and (e) dementia. Error bars indicate SEM. *p≤0.05 indicates significance; **p≤0.01 indicates highly significant. Abbreviations: ANOVA, analysis of variance; SEM, standard error of the mean; NKA, Na⁺/K⁺-ATPase; SPTA, α-spectrin; PD, Parkinson’s disease; ALS, amyotrophic lateral sclerosis; DM, dementia.