Author(s): Tamilselvan. M, Tamilanban. T, V. Chitra

Email(s): tamil251997@gmail.com

DOI: 10.5958/0974-360X.2020.00534.X   

Address: Tamilselvan. M*, Tamilanban. T, V. Chitra
Department of Pharmacology, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chengalpet- 603203.
*Corresponding Author

Published In:   Volume - 13,      Issue - 6,     Year - 2020


ABSTRACT:
Dementia also termed as memory loss is due to the functional impairment of behavior and cognition in people aged 65 years and above. Alzheimer's disease (AD) is the most occurring neurodegenerative disorder around the globe and its estimated that about 47 million people are affected by this disease and is expected to increase to 62% by the end of 2030. It is characterized by the intracellular neuro-fibrillary tangles, extracellular amyloid plaques, and deficiency cholinergic neurons and cholinergic transmission. Alzheimer’s disease is due to many reasons. The early-onset Alzheimer’s disease, an uncommon form of disease, which pursues an autosomal- dominant model in most of cases with mutations recognized in amyloid precursor protein (APP), presenilin (PS) 1 and 2. The late- onset Alzheimer’s disease, an erratic form of disease, which affects over 90% of patients with different genetic makeup and the associated risk factors are studied by different genetic studies and bio-informatic methods. These findings gave us deeper insights about the pathogenesis of Alzheimer’s disease and also in the advancement of newer therapeutic pathways and clinical trial designs. Presently available drugs are gives only symptomatic relief to the patients such as reversible acetylcholinestrase inhibitors Donepezil, Rivastigmine, Galantamine and N-methyl D-aspartate receptor antagonist like Memantine. Many compounds are still under preclinical and clinical studies focusing on the pathology of Alzheimer’s. The Recent studies target the formation and aggregation of amyloid plaques, inhibition of tau formation, stabilization of tau proteins, gene therapy and stem cell therapy. In this review summarises the current management and new approaches in the management of Alzheimer’s disease.


Cite this article:
Tamilselvan. M, Tamilanban. T, V. Chitra. Unfolding Remedial Targets for Alzheimer’s Disease. Research J. Pharm. and Tech 2020; 13(6): 3021-3027. doi: 10.5958/0974-360X.2020.00534.X


REFERENCE:
1.    K. Blennow, M.J. de Leon, H. Zetterberg, Alzheimer's disease, Lancet 368 (2006) 387e403.
2.    Chiang K, Koo EH. Emerging therapeutics for Alzheimer’s dis-ease. Annu Rev Pharmacol Toxicol. 2014; 54:381—405.
3.    Francis PT, Nordberg A, Arnold SE. A preclinical view of cholinesterase inhibitors in neuroprotection: Do they providemore than symptomatic benefits in Alzheimer’s disease. Trends Pharmacol Sci. 2005; 26:104—11.
4.    Huansg Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell. 2012; 148:1204—22.
5.    Olton DS, Becker JT, Handelmann GE. Hippocampus, space, and memory. Behav. Brain Sci. 1979; 2:313-365.
6.    Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science. 1992; 256:184—5.
7.    Haass C, Kaether C, Thinakaran G, Sisodia S. Trafficking and proteolytic processing of APP. Cold Spring Harb Perspect Med.2012; 2:a006270.
8.    Hernández F, Avila J. "Tauopathies". Cell. Mol. Life Sci. 2007; 64 (17): 2219–33.
9.    Takada Y, Yonezawa A, Kume T et al.: Nicotinic acetylcholine receptor mediated neuroprotection by donepezil against glutamate neurotoxicity in ratcortical neurons. J. Pharmacol. Exp. Ther.(2003) 306(2):772-777.
10.    Svensson AL, Nordberg A: Tacrine and donepezil attenuate the neurotoxic effects of A beta(25-35) in rat PC12 cells. Neuroreport (1998) 9(7):1519-1522.
11.    Racchi M, Mazzucchelli M, Porrello E, Lanni C, Govoni S: Acetylcholinesterase inhibitors: novel activities of old molecules. Pharmacol. Res.(2004) 50(4):441-451.
12.    Rogers SL, Friedhoff LT; Donepezil Study Group: The efficacy and safety of donepezil in patients with Alzheimer’s disease: results of a US multicentre, randomiozed, double-blind, placebo-controlled trial. The Donepezil Study Group. Dementia (1996)7(6):293-303.
13.    Rogers SL, Farlow MR, Doody RS et al.: A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease. Neurology (1998)50(1):136-145.
14.    Burns A, Rossor M, Hecker J et al.: The effects of donepezil in Alzheimer’s disease – results from a multinational trial. Dement. Geriatr. Cogn. Disord. (1999)10(3):237-244.
15.    Winblad B, Grossberg G, Frölich L, et al., IDEAL: a 6-month, double-blind, placebo-controlled study of the first skin patch for Alzheimer disease, Neurology, 2007;69(4 Suppl. 1):S14–22.
16.    Winblad B, Kawata AK, Beusterien KM, et al., Caregiver preference for rivastigmine patch relative to capsules fortreatment of probable Alzheimer’s disease, Int J Geriatr Psychiatry, 2007;22(5):485–91.
17.    Grossberg G, Sadowsky C, Förstl H, et al., Safety and tolerability of the rivastigmine patch: results of a 28-weekopen-label extension, Alzheimer Dis Assoc Disord, 2008;
18.    Bickel U, Thomsen T, Weber W, et al. Pharmacokinetics of galantamine in humans and corresponding cholinesterase inhibition. Clin Pharmacol Ther 1991; 50:420–428.
19.    Mihailova D, Yamboliev I, Zhivkova Z, Tencheva J, Jovovich V. Pharmacokinetics of galantamine hydrobromide after single subcutaneous and oral dosage in humans. Pharmacology 1989; 39:50–58.
20.    European Medicines Agency. Ebixa. European Public Assess-Report. [online]. Jul 2002. Available from: http://ww- tection w.emea.eu.int/humandocs/PDFs/EPAR/ebixa [Accessed 22 Feb 2005].
21.    Schugens MM, Egerter R, Daum I, et al. The NMDA antagonist well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist: a review of preclinical data. Neuropharmacology 1999 Neurosci Lett 1997 Mar 7; 224 (1): 57-60
22.    Thies W, Bleiler L. Alzheimer’s Association. 2013 Alzheimer’s disease facts and figures. Alzheimers Dement. 2013; 9:208—45.
23.    Chiang K, Koo EH. Emerging therapeutics for Alzheimer’s dis-ease. Annu Rev Pharmacol Toxicol. 2014; 54:381—405.
24.    Francis PT, Nordberg A, Arnold SE. A preclinical view of cholinesterase inhibitors in neuroprotection: Do they providemore than symptomatic benefits in Alzheimer’s disease. Trends Pharmacol Sci. 2005; 26: 104—11.
25.    Vassar R, Kandalepas PC. The secretase enzyme BACE1 asa therapeutic target for Alzheimer’s disease. Alzheimer’s ResTher. 2011; 3:20.
26.    Menting KW, Claassen JA. Secretase inhibitor; a promising novel therapeutic drug in Alzheimer’s disease. Front Aging Neu-rosci. 2014;6:165
27.    Yan R, Vassar R. Targeting the secretase BACE1 for Alzheimer’s disease therapy. Lancet Neurol. 2014; 13:319—29.
28.    Chiang K, Koo EH. Emerging therapeutics for Alzheimer’s dis-ease. Annu Rev Pharmacol Toxicol. 2014; 54:381—405.20. Imbimbo BP, Giardina GA.  Secretase inhibitors and modulatorsfor the treatment of Alzheimer’s disease: disappointments andhopes. Curr Top Med Chem. 2011; 11:1555—70.
29.    Wolfe MS.  Secretase as a target for Alzheimer’s disease. AdvPharmacol. 2012; 64:127—53.
30.    Obregon DF, Rezai-Zadeh K, Bai Y, Sun N, Hou H, EhrhartJ, et al. ADAM10 activation is required for green tea(−)-epigallocatechin-3-gallate-induced alpha-secretase cleav-age of amyloid precursor protein. J Biol Chem. 2006;281:16419—
31.    Etcheberrigaray R, Tan M, Dewachter I, Kuipéri C, van der Auw-era I, Wera S, et al. Therapeutic effects of PKC activators in Alzheimer’s disease transgenic mice. Proc Natl Acad Sci U S A.2004; 101:11141—6.
32.    Gauthier S, Aisen PS, Ferris SH, Saumier D, Duong A, HaineD, et al. Effect of tramiprosate in patients with mild-to-moderate Alzheimer’s disease: Exploratory analyses of the MRIsub-group of the Alphase study. J Nutr Health Aging. 2009; 13:550—7.
33.    Aisen PS, Gauthier S, Ferris SH, Saumier D, Haine D, Garceau D, et al. Tramiprosate in mild-to-moderate Alzheimer’s disease —–a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study). Arch Med Sci. 2011; 7:102—11
34.    Nalivaeva NN, Fisk LR, Belyaev ND, Turner AJ. Amyloid-degrading enzymes as therapeutic targets in Alzheimer’sdisease. Curr Alzheimer Res. 2008; 5:212—24.
35.    Higuchi M, Iwata N, Saido TC. Understanding molecular mechanisms of proteolysis in Alzheimer’s disease: Progresstoward therapeutic interventions. Biochim Biophys Acta.2005;1751:60—7.
36.    Muhs A, Hickman DT, Pihlgren M, Chuard N, Giriens V, Meer-schman C, et al. Liposomal vaccines with conformation-specificamyloid peptide antigens define immune response and efficacy in APP transgenic mice. Proc Natl Acad Sci U S A.2007; 104:9810—5.
37.    Liu B, Frost JL, Sun J, Fu H, Grimes S, Blackburn P, et al. MER5101, a novel A _1-15:DT conjugate vaccine, generates arobust anti-A _ antibody response and attenuates A pathology and cognitive deficits in APPswe/PS1 _E9 transgenic mice. J Neurosci. 2013; 33:7027—37.
38.    Panza F, Solfrizzi V, Imbimbo BP, Logroscino G. Amyloid-directed monoclonal antibodies for the treatment of Alzheimer’sdisease: the point of no return. Expert Opin Biol Ther.2014;14:1465—76.
39.    Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. BrainRes Brain Res Rev. 2000; 33:95–130.Cao et al. Molecular Neurodegeneration (2018) 13:64 Page 14 of 20
40.    Drechsel DN, Hyman AA, Cobb MH, Kirschner MW. Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau. Mol Biol Cell. 1992; 3:1141–54.
41.    Hung SY, Fu WM. Drug candidates in clinical trials for Alzheimer's disease. JBiomed Sci. 2017; 24:47.
42.    Pei JJ, Bjorkdahl C, Zhang H, Zhou X, Winblad B. p70 S6 kinase and tau in Alzheimer's disease. J Alzheimers Dis. 2008; 14:385–92.
43.    Jia Q, Deng Y, Qing H. Potential therapeutic strategies for Alzheimer's disease targeting or beyond beta-amyloid: insights from clinical trials. Biomed Res Int. 2014;2014:837157.
44.    Flight MH. Neurodegenerative disease: tau immunotherapy targets transcellular propagation. Nat Rev Drug Discov. 2013; 12:904.
45.    Goedert M, Eisenberg DS, Crowther RA. Propagation of tau aggregates and neurodegeneration. Annu Rev Neurosci. 2017; 40:189–210.
46.    Goedert M, Spillantini MG. Propagation of tau aggregates. Mol Brain. 2017;10:18.
47.    Kfoury N, Holmes BB, Jiang H, Holtzman DM, Diamond MI. Trans-cellular propagation of tau aggregation by fibrillar species. J Biol Chem. 2012; 287:19440–51.
48.    Wu J., Li Q., Bezprozvanny I. Evaluation of Dimebon in cellular model of Huntington's disease. Molecular Neurodegeneration 2008; 3: 15.
49.    Braddock M. Safely slowing down the decline in Alzheimer’s disease: gene therapy shows potential. Expert Opin Investig Drugs. 2005; 14:913–5.
50.    Siemer E, Skinner M, Dean RA, Conzales C, Satterwhite J, Farlow M, Ness D, May PC. Safety, tolerability, and changes in amyloid beta concentrations after administration of a gamma-secretase inhibitor in volunteers. Clin Neuropharmacol. 2005; 28:126–32.
51.    Alzheimer's and Dementia: The Journal of the Alzheimer's Association 2014; 10 (5): 571–581.
52.    Weiss, S., Dunne, C., Hewson, J., et al. Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J. Neurosci. 1996; 16: 7599–7609.
53.    Dr. Ulrich Werth Makes a Good Point; Journal of Longevity; 2008; Vol. 14 / No. 2
54.    Tarkowski E, Liljeroth AM, Minthon L, Tarkowski A, Wallin A, Blennow K: Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res Bull 2003; 61(3): 255-60.
55.    Tancredi V, D'Arcangelo G, Grassi F, Tarroni P, Palmieri G, Santoni A, Eusebi F: Tumor necrosis factor alters synaptic transmission in rat hippocampal slices. Neurosci Lett 146(2):176-8.1992 Nov 9.
56.    Freiherr J, Hallschmid M, Frey WH, Brunner YF, Chapman CD, Holscher C, Craft S, De Felice FG, Benedict C. Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence. CNS Drugs 2013; 27(7): 505-14.
57.    Marx, C, Trost, W, Shampine, L, Stevens, R, Hulette, C, Steffens, D, Ervin, J, Butterfield, M et al. The Neurosteroid Allopregnanolone Is Reduced in Prefrontal Cortex in Alzheimer's Disease". Biological Psychiatry 2006; 60(12): 1287–94.

Recomonded Articles:

Author(s): Leelavathi D Acharya, N R Rau, N Udupa, Surulivel Rajan M, Vijayanarayana K

DOI: 10.5958/0974-360X.2016.00162.1         Access: Open Access Read More

Author(s): Jyothi.S, Karthikeyan Murthykumar, Anupama Deepak, Dhanraj, Noorul Aneesa, Sowndarya Baskar, Lakshya Rani

DOI: 10.5958/0974-360X.2016.00113.X         Access: Open Access Read More

Author(s): M. Dilip Kumar

DOI: Not Available         Access: Open Access Read More

Author(s): R. S. Adnaik, P. S. Gavarkar, S. K. Mohite, C, S Magdum

DOI: Not Available         Access: Open Access Read More

Author(s): Ghadge Ojaswi, Nadar Divya, Parmar Digna

DOI: 10.5958/0974-360X.2016.00107.4         Access: Open Access Read More

Author(s): Mrunmayee P. Toraskar, Vinayak G. Pande, Ashwini Kulkarni, Vilasrao J. Kadam

DOI: Not Available         Access: Open Access Read More

Author(s): Neveda Baskeran

DOI: Not Available         Access: Open Access Read More

Author(s): Vasudev Pai, Chandrashekar K. S, C. S. Shreedhara, Aravinda Pai

DOI: 10.5958/0974-360X.2017.00628.X         Access: Open Access Read More

Author(s): Rakesh Singh, Swarnlata Saraf

DOI:         Access: Open Access Read More

Author(s): Jayalakshmi N, Ranadheer Chowdary. P, Praveen. D, M. Vijey Aanandhi

DOI: 10.5958/0974-360X.2018.00282.2         Access: Open Access Read More

Author(s): Jagadeesan M, Manikandan R, Nandamuri Sri Sai Sudha

DOI: 10.5958/0974-360X.2018.00565.6         Access: Open Access Read More

Author(s): S. Lakshmi kanthamma, Joyita Kriszhnamurthi, C. N. Hemalatha, M. Vijey Aanandhi

DOI: 10.5958/0974-360X.2018.00283.4         Access: Open Access Read More

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

0.38
2018CiteScore
 
56th percentile
Powered by  Scopus


SCImago Journal & Country Rank


Recent Articles




Tags